Antigenic polypeptides

ABSTRACT

The invention relates to a method for the identification of antigenic polypeptides expressed by pathogenic microbes; vaccines comprising said polypeptides; recombinant methods to manufacutre said polypeptides; and therapeutic antibodies directed to said polypeptides.

[0001] The invention relates to a method for the identification ofantigenic polypeptides expressed by pathogenic microbes; vaccinescomprising said polypeptides; recombinant methods to manufacture saidpolypeptides; and therapeutic antibodies directed to said polypeptides.

[0002] Microbial organisms cause a number of fatal or debilitatingdiseases which affect many millions of people around the world.Currently methods to control microbial organisms include the use ofantimicrobial agents (antibiotics) and disinfectants. These have provedto be problematic since exposure to these agents places a significantselection pressure resulting in the creation of resistant microbes whichcan avoid the effects of the antimicrobial agent(s). For example,recently it has been discovered that microbial organisms have becomeresistant to triclosan, an agent added to many disinfectants used inhouseholds and industrial environments.

[0003] An arguably greater problem is the evolution of antibioticresistant strains of a number of significant pathogenic microbes.

[0004] For example, and not by way of limitation, it is estimated thatthere are up to 50 million people world-wide infected with drugresistant tuberculosis (TB) (Figures from the World Health Organisation,1998). In the past the use of antibiotics to treat TB relied on theadministration of single drugs (eg ethionamide) which promoted arelatively high frequency of resistance. For this reason, combinationsof drugs are now used to treat tuberculosis. However the fatality ratein cases caused by strains that are resistant to at least one drug usedto treat tuberculosis still approaches 50% even when treatment is given.Mycobacteriumn tuberculosis, the causative agent of TB, is a slowgrowing bacteria and takes a long time to kill. Therefore, for a drugcombination to be effective a person with TB must take the drugcombination daily for at least six months. Accordingly, patientsfrequently have to take two or more pills daily and this requires aregimented dosage over a relatively long period of treatment. Manypatients take the medications only intermittently and therefore do notfinish the full course of therapy to completely eradicate the M.tuberculosis infection. Moreover, TB is strongly associated with HTinfection and therefore the establishment of TB is strongly correlatedwith immunosuppression.

[0005] Vaccination against TB has been available for many years. Thebacillus calmette and guerin (BCG) vaccination has been widely usedthroughout the world for a long time because it is a safe andinexpensive means to vaccinate large numbers of people who potentiallycould contract TB. BCG is derived from live, attenuated strains ofMycobacterium bovis. However the impact of vaccination on the infectiousforms of TB is minimal and BCG has therefore contributed little to theoverall control of the disease.

[0006] A further example of a pathogenic organism which has developedresistance to antibiotics is Staphylococcus aureus. S. aureus is abacterium whose normal habitat is the epithelial lining of the nose inabout 20-40% of normal healthy people and is also commonly found onpeople's skin usually without causing harm. However, in certaincircurmstances, particularly when skin is damaged, this germ can causeinfection. This is a particular problem in hospitals where patients mayhave surgical procedures and/or be taking immunosuppressive drugs. Thesepatients are much more vulnerable to infection with S. aureus because ofthe treatment they have received. Resistant strains of S. aureus havearisen in recent years. Methicillin resistant strains are prevalent andmany of these resistant strains are also resistant to several otherantibiotics. Currently there is no effective vaccination procedure forS. aureus. In the US, S. aureus infections are the cause of 13% of thetwo million hospitalised infections each year. This represents 260,000people with an infection of S. aureus, of which 60-80,000 die.

[0007]S. aureus is therefore a major human pathogen capable of causing awide range of life threatening diseases including septicaemia,endocarditis, arthritis and toxic shock. This ability is determined bythe versatility of the organism and its arsenal of components involvedin virulence. Pathogenicity is multifactorial and no one component hasshown to be responsible for a particular infection, see Projan, S. J. &Novick, R. P. (1997) in The Staphylococci in Human Disease (Crossley, K.B. & Archer, G. L., eds.) pp.55-81.

[0008] At the onset of infection, and as it progresses, the needs andenvironment of the organism changes and this is mirrored by acorresponding alteration in the virulence determinants which S. aureusproduces. At the beginning of infection it is important for the pathogento adhere to host tissues and so a large repertoire of cell surfaceassociated attachment proteins are made. These include collagen-,fibrinogen- and fibronectin-binding proteins. The pathogen also has theability to evade host defences by the production of factors that reducephagocytosis or interfere with the ability of the cells to be recognisedby circulating antibodies.

[0009] Often a focus of infection develops as an abscess and the numberof organisms increases. S. aureus has the ability to monitor its owncell density by the production of a quorum sensing peptide. Accumulationof the peptide, associated with physiological changes brought about bythe beginning of starvation of the cells, elicits a switch in virulencedeterminant production from adhesins to components involved in invasionand tissue penetration. These include a wide range of hemolysins,proteases and other degradative enzymes.

[0010] During the process of any infection the virulence determinantsmade by S. aureus are produced in response to environmental andphysiological stimuli. These stimuli will be dependent on the nichewithin the body and will change as the infection progresses. Little isknown of the conditions in vivo and it is likely that some componentsare produced solely in this environment. These are therefore potentialvaccine components, which could not be discovered by previoustechniques.

[0011] One of the most important developments in recent medical historyis the development of vaccines which provide prophylactic protectionfrom a wide variety of pathogenic organisms. Many vaccines are producedby inactivated or attenuated pathogens which are injected into anindividual. The immunised individual responds by producing both ahumoral (antibody) and cellular (cytolytic T cells, CTL's) response. Forexample, hepatitis vaccines are made by heat inactivating the virus andtreating it with a cross linking agent such as formaldehyde. An exampleof an attenuated pathogen useful as a vaccine is represented by poliovaccines which are produced by attenuating a live pathogen.

[0012] However the use of attenuated organisms in vaccines for certaindiseases is problematic due to the lack of knowledge regarding thepathology of the condition and the nature of the attenuation. Forcertain viral agents this is a particular problem since viruses, inparticular retroviruses, have an error prone replication cycle whichresults viable mutations in the genes which comprise the virus. This canresult in alterations to antigenic determinants which have previouslybeen used as vaccines. An alternative to the use of inactivated orattenuated pathogens is the identification of pathogen epitopes to whichthe immune system is particularly sensitive. In this regard manypathogenic toxins produced by pathogenic organisms during an infectionare particularly useful in the development of vaccines which protect theindividual from a particular pathogenic organism.

[0013] The development of so-called subunit vaccines (vaccines in whichthe immunogen is a fragment or subunit of a protein or complex expressedby a particular pathogenic organism) has been the focus of considerablemedical research. The need to identify candidate molecules useful in thedevelopment of subunit vaccines is apparent not least becauseconventional chemotherapeutic approaches to the control of pathogenicorganisms has more recently been stymied by the development ofantibiotic resistance. A number of methods have been developed toidentify potential antigenic polypeptides which can be used as avaccine. One such method is disclosed herein.

[0014] It has been known for many years that tumour cells produce anumber of tumour cell specific antigens, some of which are presented atthe tumour cell surface. The immune system recognises these antigens asforeign thereby resulting in the production of antibodies to selfantigens, so called autoantibodies or autologous antisera.

[0015] One such technique is Serological identification of antigens byrecombinant Expression Cloning, abbreviated to SEREX.

[0016] Typically, the technique involves the extraction of RNA fromtumour tissue followed by the selective enrichment of mRNA from theisolated total RNA. The mRNA is reverse transcribed into cDNA usingviral reverse transcriptase. The cDNA thus synthesised is subcloned intoan expression vector and transformed into an appropriate bacterialstrain. The transformed bacteria are plated onto a suitable nutrientagar and under appropriate growth conditions the subcloned cDNA isexpressed from the expression vector in the bacterial cell. The cellsare lysed naturally by the use of phage based expression vectors, forexample λ phage or phagemid based vectors, which through their lyticcycle cause cell lysis. The released polypeptides are transferred to asuitable membrane support (i.e. nitrocellulose, nylon) and exposed toautologous antisera from the patient from which the tumour tissue wasoriginally isolated. The immunoscreening methodology allows theidentification of genes that are over expressed or inappropriatelyexpressed in a selected tumour tissue from a patient.

[0017] We have exploited this techinque to identify antigenicpolypeptides expressed by pathogenic organisms during an infection.Autologous antisera produced during the infection is used to screen anexpression library created from genomic DNA to identify and cloneantigens.

[0018] In its broadest aspect the invention relates to theidentification of antigenic polypeptides expressed during an infectionby a pathogenic microbe.

[0019] According to a first aspect of the invention there is provided amethod to identify antigenic polypeptides comprising:

[0020] (i) providing a nucleic acid library encoding genes or partialgene sequences of a pathogenic organism;

[0021] (ii) transforming/transfecting said library into a host cell;

[0022] (iii) providing conditions conducive to the expression of saidtransformed/transfected genes or partial gene sequences;

[0023] (iv) contacting the polypeptides expressed by the genes/partialgene sequences with autologous antisera derived from an animal infectedwith, or has been infected with, said pathogenic organism; and

[0024] (v) purifying the nucleic acid encoding the polypeptide orpartial polypeptide binding to said autologous antisera.

[0025] In a preferred method of the invention said library comprisesgenomic DNA of a pathogenic organism.

[0026] Ideally said pathogenic organism is bacterial.

[0027] More preferably still said bacterial organism is selected fromthe following: Staphylococcus aureus; Staphylococcus epidermidis;Enterococcus faecalis; Mycobacteriuin tuberculsis; Streptococcus groupB; Streptoccocus pneumoniae; Helicobacter pylori; Neisseria gonorrhea;Streptococcus group A; Borrelia burgdorferi; Coccidiodes immitis;Histoplasma sapsulatum; Neisseria meningitidis type B; Shigellaflexneri; Escherichia coli; Haemophilus influenzae.

[0028] Preferably still said pathogenic organism is of the genusStaphylococcus spp. Ideally organism is Staphlococcus aureus orStaphylococcus epidermidis.

[0029] In a further preferred embodiment of the invention said nucleicacid library is a lambda library, ideally a lambda expression library.

[0030] According to a second aspect of the invention there is provided anucleic acid molecule comprising a DNA sequence selected from:

[0031] (i) the DNA sequence as represented in SEQ ID NO's 1-13;

[0032] (ii) DNA sequences which hybridise to the sequence presented inthe SEQ ID No's 1-13 identified in (i) above which encode a polypeptideexpressed by a pathogenic organism and

[0033] (iii) DNA sequences which are degenerate as a result of thegenetic code to the DNA sequences defined in (i) and (ii).

[0034] In a yet still further preferred embodiment of the invention saidnucleic acid molecule is genomic DNA.

[0035] In a preferred embodiment of the invention there is provided anisolated nucleic acid molecule which anneals under stringenthybridisation conditions to the sequences presented in SEQ ID NO's 1-13.

[0036] Stringent hybridisation/washing conditions are well known in theart. For example, nucleic acid hybrids that are stable after washing in0.1×SSC, 0.1% SDS at 60° C. It is well known in the art that optimalhybridisation conditions can be calculated if the sequences of thenucleic acid is known. For example, hybridisation conditions can bedetermined by the GC content of the nucleic acid subject tohybridisation. Please see Sambrook et al (1989) Molecular Cloning; ALaboratory Approach. A common formula for calculating the stringencyconditions required to achieve hybridisation between nucleic acidmolecules of a specified homology is:

T _(m)=81.5° C.+16.6 Log[Na ⁺]+0.41[% G+C]−0.63 (% formamide).

[0037] According to a third aspect of the invention there is provided atleast one polypeptide identified by the method according to theinvention.

[0038] In a preferred embodiment of the invention, said polypeptide isassociated with infective pathogenicity of an organism according to anyprevious aspect or embodiment of the invention.

[0039] More preferably still said polypeptide is at least one, or partof SEQ ID NO's: 14-19.

[0040] According to a fourth aspect of the invention there is provided anucleic acid molecule characterised in that said nucleic acid moleculeis part of a vector adapted to facilitate recombinant expression of thepolypeptide encoded by said nucleic acid molecule.

[0041] In a preferred embodiment of the invention said vector is anexpression vector adapted for prokaryotic gene expression. Alternativelysaid expression vector is adapted for eukaryotic gene expression.

[0042] Typically said adaptation includes, by example and not by way oflimitation, the provision of transcription control sequences (promotersequences) which mediate cell specific expression. These promotersequences may be cell specific, inducible or constitutive.

[0043] Promoter is an art recognised term and, for the sake of clarity,includes the following features which are provided by example only, andnot by way of limitation. Enhancer elements are cis acting nucleic acidsequences often found 5′ to the transcription initiation site of a gene(enhancers can also be found 3′ to a gene sequence or even located inintronic sequences and is therefore position independent). Enhancersfunction to increase the rate of transcription of the gene to which theenhancer is linked. Enhancer activity is responsive to trans actingtranscription factors (polypeptides) which have been shown to bindspecifically to enhancer elements. The binding/activity of transcriptionfactors (please see Eukaryotic Transcription Factors, by David SLatchman, Academic Press Ltd, San Diego) is responsive to a number ofenvironmental cues which include, by example and not by way oflimitation, intermediary metabolites (eg glucose, lipids), environmentaleffectors (eg light, heat).

[0044] Promoter elements also include so called TATA box and RNApolymerase initiation selection (RIS) sequences which function to selecta site of transcription initiation. These sequences also bindpolypeptides which function, inter alia, to facilitate transcriptioninitiation selection by RNA polymerase.

[0045] Adaptations also include the provision of selectable markers andautonomous replication sequences which both facilitate the maintenanceof said vector in either the eukaryotic cell or prokaryotic host.Vectors which are maintained autonomously are referred to as episomalvectors.

[0046] Adaptations which facilitate the expression of vector encodedgenes include the provision of transcription termination/polyadenylationsequences. This also includes the provision of internal ribosome entrysites (IRES) which function to maximise expression of vector encodedgenes arranged in bicistronic or multi-cistronic expression cassettes.

[0047] These adaptations are well known in the art. There is asignificant amount of published literature with respect to expressionvector construction and recombinant DNA techniques in general. Pleasesee, Sambrook et al (1989) Molecular Cloning: A Laboratory Manual, ColdSpring Harbour Laboratory, Cold Spring Harbour, N.Y. and referencestherein; Marston, F (1987) DNA Cloning Techniques: A Practical ApproachVol III In Press, Oxford UK; DNA Cloning: F M Ausubel et al, CurrentProtocols in Molecular Biology, John Wiley & Sons, Inc. (1994).

[0048] According to yet a further aspect of the invention there isprovided a method for the production of the polypeptides according toany previous aspect or embodiment of the invention comprising:

[0049] (i) providing a cell transformed/transfected with a vectoraccording to the invention;

[0050] (ii) growing said cell in conditions conducive to the manufactureof said polypeptides; and

[0051] (iii) purifying said polypeptide from said cell, or its growthenvironment.

[0052] In a preferred method of the invention said vector encodes, andthus said recombinant polypeptide is provided with, a secretion signalto facilitate purification of said polypeptide.

[0053] According to a fifth aspect of the invention there is provided acell or cell-line transformed or transfected with the vector accordingto the invention.

[0054] In a preferred embodiment of the invention said cell is aprokaryotic cell. Alternatively said cell is a eukaryotic cell selectedfrom: fungal, insect, amphibian; mammalian; plant.

[0055] According to a yet further aspect of the invention there isprovided a vaccine comprising at least one polypeptide according to theinvention.

[0056] Ideally said vaccine further comprises a carrier and/or adjuvant.

[0057] The terms adjuvant and carrier are construed in the followingmanner. Some polypeptide or peptide antigens contain B-cell epitopes butno T cell epitopes. lmmune responses can be greatly enhanced by theinclusion of a T cell epitope in the polypeptide/peptide or by theconjugation of the polypeptide/peptide to an immunogenic carrier proteinsuch as key hole limpet haemocyanin or tetanus toxoid which containmultiple T cell epitopes. The conjugate is taken up by antigenpresenting cells, processed and presented by human leukocyte antigens(HLA's) class II molecules. This allows T cell help to be given by Tcell's specific for carrier derived epitopes to the B cell which isspecific for the original antigenic polypeptide/peptide. This can leadto increase in antibody production, secretion and isotype switching.

[0058] An adjuvant is a substance or procedure which augments specificimmune responses to antigens by modulating the activity of immune cells.Examples of adjuvants include, by example only, agonsitic antibodies toco-stimulatory molecules, Freunds adjuvant, muramyl dipeptides,liposomes. An adjuvant is therefore an immunomodulator. A carrier is animmunogenic molecule which, when bound to a second molecule augmentsimmune responses to the latter.

[0059] In yet a further aspect of the invention there is provided amethod to immunise an animal against a pathogenic microbe comprisingadministering to said animal at least one polypeptide, or part thereof,according to the invention or the vaccine according to the invention.

[0060] In a preferred method of the invention said animal is human.

[0061] Preferably the vaccine, or antigenic polypeptide, can bedelivered by direct injection either intravenously, intramuscularly,subcutaneously. Further still, the vaccine or antigenic polypeptide, maybe taken orally.

[0062] Preferably the vaccine is against the bacterial speciesStaphylococcus aureus.

[0063] The vaccine may also be against the bacterial speciesStaphylococcus epidermidis.

[0064] It will also be apparent that vaccines or antigenic polypeptidesare effective at preventing or alleviating conditions in animals otherthan humans, for example and not by way of limitation, family pets,livestock, horses.

[0065] According to a further aspect of the invention there is providedan antibody, or at least an effective binding part thereof, which bindsat least one polypeptide according to the invention.

[0066] In a preferred embodiment of the invention said antibody is apolyclonal or monoclonal antibody wherein said antibody is specific tosaid polypeptide.

[0067] Alternatively, said antibody is a chimeric antibody produced byrecombinant methods to contain the variable region of said antibody withan invariant or constant region of a human antibody.

[0068] In a further alternative embodiment of the invention, saidantibody is humanised by recombinant methods to combine thecomplimentarity determining regions of said antibody with both theconstant (C) regions and the framework regions from the variable (V)regions of a human antibody.

[0069] Preferably said antibody is provided with a marker including aconventional label or tag, for example a radioactive and/or fluorescentand/or epitope label or tag.

[0070] Preferably said humanised monoclonal antibody to said polypeptideis produced as a fusion polypeptide in an expression vector suitablyadapted for transfection or transformation of prokaryotic or eukaryoticcells.

[0071] Antibodies, also known as immunoglobulins, are protein moleculeswhich have specificity for foreign molecules (antigens). lmmunoglobulins(Ig) are a class of structurally related proteins consisting of twopairs of polypeptide chains, one pair of light (L) (low molecularweight) chain (κ or λ), and one pair of heavy (H) chains (γ, α, μ, δ andε), all four linked together by disulphide bonds. Both H and L chainshave regions that contribute to the binding of antigen and that arehighly variable from one Ig molecule to another. In addition, H and Lchains contain regions that are non-variable or constant.

[0072] The L chains consist of two domains. The carboxy-terminal domainis essentially identical among L chains of a given type and is referredto as the “constant” (C) region. The amino terminal domain varies from Lchain to L chain and contributes to the binding site of the antibody.Because of its variability, it is referred to as the “variable” (V)region.

[0073] The H chains of Ig molecules are of several classes, α, μ, σ, α,and γ (of which there are several sub-classes). An assembled Ig moleculeconsisting of one or more units of two identical H and L chains, derivesits name from the H chain that it possesses. Thus, there are five Igisotypes: IgA, IgM, IgD, IgE and IgG (with four sub-classes based on thedifferences in the H chains, i.e., IgG1, IgG2, IgG3 and IgG4). Furtherdetail regarding antibody structure and their various functions can befound in, Using Antibodies: A laboratory manual, Cold Spring HarbourLaboratory Press.

[0074] Chimeric antibodies are recombinant antibodies in which all ofthe V-regions of a mouse or rat antibody are combined with humanantibody C-regions. Humanised antibodies are recombinant hybridantibodies which fuse the complimentarity determining regions from arodent antibody V-region with the framework regions from the humanantibody V-regions. The C-regions from the human antibody are also used.The complimentarity determining regions (CDRs) are the regions withinthe N-terminal domain of both the heavy and light chain of the antibodyto where the majority of the variation of the V-region is restricted.These regions form loops at the surface of the antibody molecule. Theseloops provide the binding surface between the antibody and antigen.

[0075] Antibodies from non-human animals provoke an immune response tothe foreign antibody and its removal from the circulation. Both chimericand humanised antibodies have reduced antigenicity when injected to ahuman subject because there is a reduced amount of rodent (i.e. foreign)antibody within the recombinant hybrid antibody, while the humanantibody regions do not illicit an immune response. This results in aweaker immune response and a decrease in the clearance of the antibody.This is clearly desirable when using therapeutic antibodies in thetreatment of human diseases. Humanised antibodies are designed to haveless “foreign” antibody regions and are therefore thought to be lessimmunogenic than chimeric antibodies.

[0076] In another aspect of the invention there is provided a vectorwhich is adapted for the expression of the humanised or chimericantibodies according to the invention.

[0077] In a yet further aspect of the invention, there is provided acell or cell line which has been transformed or transfected with thevector encoding the humanised or chimeric antibody according to theinvention.

[0078] In a yet further aspect of the invention there is provided amethod for the production of the humanised or chimeric antibodyaccording to the invention comprising:

[0079] (i) providing a cell transformed or transfected with a vectorwhich comprises a nucleic acid molecule encoding the humanised orchimeric antibody according to the invention;

[0080] (ii) growing said cell in conditions conducive to the manufactureof said antibody; and

[0081] (iii) purifying said antibody from said cell, or its growthenvironment.

[0082] In a yet further aspect of the invention there is provided ahybridoma cell line which produces a monoclonal antibody as hereinbeforedescribed.

[0083] In a further aspect of the invention there is provided a methodof producing rmonoclonal antibodies according to the invention usinghybridoma cell lines according to the invention.

[0084] In a further aspect of the invention there is provided a methodfor preparing a hybridoma cell-line producing monoclonal antibodiesaccording to the invention comprising the steps of:

[0085] i) immunising an immunocompetent mammal with an immunogencomprising at least one polypeptide having the amino acid sequence asrepresented in SEQ. ID No 14-19, or fragments thereof;

[0086] ii) fusing lymphocytes of the immunised immunocompetent mammalwith myeloma cells to form hybridoma cells;

[0087] iii) screening monoclonal antibodies produced by the hybridomacells of step (ii) for binding activity to the amino acid sequences of(i);

[0088] iv) culturing the hybridoma cells to proliferate and/or tosecrete said monoclonal antibody; and

[0089] v) recovering the monoclonal antibody from the culturesupernatant.

[0090] Preferably, the said immunocompetent mammal is a mouse.Alternatively, said immunocompetent mammal is a rat.

[0091] The production of monoclonal antibodies using hybridoma cells iswell-known in the art. The methods used to produce monoclonal antibodiesare disclosed by Kohler and Milstein in Nature 256, 495-497 (1975) andalso by Donillard and Hoffman, “Basic Facts about Hybridomas” inCompendium of Immunology V.II ed. by Schwartz, 1981, which areincorporated by reference.

[0092] In a further aspect of the invention there is provided the use ofthe antibodies for manufacture of a medicament for the treatment ofStaphylococcus aureus-associated septicaemia, food-poisoning or skindisorders.

[0093] In another aspect of the invention there is provided the use ofthe antibodies according to the invention for the manufacture of amedicament for the treatment of Staphylococcus epidermidis-associatedsepticaemia, peritonitis or endocarditis.

[0094] It will be apparent that the polypeptides identified by themethod according to the invention will facilitate the production oftherapeutic antibodies to a range of diseases resulting from pathogenicinfection, for example, septicaemia; tuberculosis; bacteria-associatedfood poisoning; blood infections; peritonitis; endocarditis; sepsis;meningitis; pneumonia; stomach ulcers; gonorrhoea; strep throat;streptococcal-associated toxic shock; necrotizing fasciitis; impetigo;histoplasmosis; Lyme disease; gastro-enteritis; dysentery; shigellosis.

[0095] As has already been stated earlier, microbial organisms cause awide variety of diseases. Listed below, and not by way of limitation,are a number of micro-organisms and some of the diseases they cause.Micro-organism Disease(s) caused Staphylococcus aureus Sepsis, foodpoisoning, septicaemia, Staphylococcus epidermidis Peritonitis,septicaemia, endocarditis, other hospital-associated diseasesEnterococcus faecalis Endocarditis, cystitis, wound infectionsMycobacterium tuberculosis Tuberculosis Streptococcus group B Sepsis,meningitis, pneumonia, bladder infections Streptococcus pneumoniaePneumonia, meningitis Helicobacter pylori Stomach ulcers Neisseriagonorrhoea Gonorrhoea Streptococcus group A Strep throat, necrotizingfasciitis, impetigo, Strep. Toxic shock syndrome Borrelia burgdoferiLyme disease Coccidiodes immitis Pneumonia Histoplasma sapsulatwnHistoplasmosis, pneumonia Neisseria meningitidis type B MeningitisShigella flexneri Gastro-enteritis, shigellosis, dysentry Escherichiacoli Food-poisoning, gastro-enteritis Haemophilus influenzae Meningitis,pneumonia, arthritis, cellulitis

[0096] An embodiment of the invention will now be described by exampleonly and with reference to the following materials, methods and SEQ IDNO's 1-19 and Table 1.

[0097] Materials and Methods

[0098] A λZAP Express library of genomic DNA of S. aureus 8325/4 wasused. It contains fragments of 2-10 kb from a partial Sau3A digest oftotal genomic DNA. This was cloned into the BamH1 site of the vector.The library contains >10× coverage of the genome. The library was probedby plaque lift using an initial screen of approximately 20,000 plaqueforming units on a 9 cm diameter Petri dish. The plating cells used,their treatment, the plating procedure and buffers were exactly asdescribed in the manufacturers handbook (Stratagene). Plating cells,Escherichia coli XL1-Blue MRF′, were infected with phage and plated in 3ml top LB agar containing 10 mM MgSO₄ onto LB plates containing 10 mMMgSO₄. The plates were then incubated at 42° C. for 4 hr. An 8.5 cmdiameter nitrocellulose filter disc (previously soaked in 10 mM IPTG andair-dried) was placed on each plate and its location marked. The plateswere then incubated for a further 3.5 hr at 37° C. The filters wereremoved and washed in TBST buffer before blocking overnight at 4° C. inTBST containing 6% w/v dried skimmed milk and 3% v/v pig serum (Sigma).The serum was used to block any Protein A clones on the filter. Thefilters are then treated with patient serum (1/5000 dilution) inblocking solution for 90 min at room temperature. Antisera have beenobtained from patients convalescing from major S. aureus infections. Thefilters are then washed for 3×10 min in TBST. Secondary antibody usedwas goat anti-human whole IgG alkaline phosphatase linked (Sigma) at1/30,000 dilution in blocking solution at room temperature for 30 min.The filters were then washed as above and developed using a standardcalorimetric procedure.

[0099] Cross-reactive plaques were located on the agar plates and coredinto 0.2 ml phage buffer with 0.02 ml chloroform. The titre of each corestock was determined and the phage plated at approximately 200 plaquesper plate. A plaque lift and screen was performed as above to givesingle, pure cross-reactive clones.

[0100] The pure clones were then spotted (1 μl) onto plates to give aconfluent plaque of 0.5 cm diameter. 30 individual clones can be spottedon each plate. A plaque lift is performed and the filter probed with anappropriate sera. In this way clones can be tested for theircross-reactivity with other patient sera, non-infected donor sera andanti-Protein A sera.

[0101] Individual clones were then excised to give a phagemid in E. coliXLOLR using the manufacturers protocol (Stratagene). A plasmid miniprepof each was carried out and the size of the genomic insert determined byrestriction mapping. The identity of the cloned insert was determined byDNA sequencing using primers against vector sequence, which allowssequencing across the insert. By comparison of the derived sequenceagainst the public domain databases the nature of the cloned gene(s) canbe determined.

[0102] Hybridisation Solutions/Conditions

[0103] Typically, hybridisation conditions uses 4-6×SSPE (20×SSPEcontains 175.3 g NaCl, 88.2 g NaH₂PO₄ H₂O and 7.4 g EDTA dissolved to 1litre and the pH adjusted to 7.4); 5-10× Denhardts solution (50×Denhardts solution contains 5 g Ficoll (type 400, Pharmacia), 5 gpolyvinylpyrrolidone abd 5 g bovine serum albumen; 100 μg-1.0 mg/mlsonicated salmon/herring DNA; 0.1-1.0% sodium dodecyl sulphate;optionally 40-60% deionised formamide. Hybridisation temperature willvary depending on the GC content of the nucleic acid target sequence butwill typically be between 42°-65° C.

[0104]Staphylococcus aureus clones identified in human sera screen TABLE1 Locus Patient Sera Clone Encoded proteins number A 1 γhemolysin B andC subunit 1 A 3 Atl 2 A 4 γhemolysin B and C subunit 1 A 5 γhemolysin Band C subunit 1 A 7 Novel putative protease (ORF1 novel 7 antigen like)A 8 Novel nuclease (YisK) 5 A 9 Novel autolysin 6 A 10 γhemolysin B andC subunit 1 A 11 Atl 2 A 14 γhemolysin B and C subunit 1 A 15 γhemolysinB and C subunit 1 A S1 Novel putative protease (ORF1 novel 7 antigenlike) A S5 Novel surface protein 12 A S17 γhemolysin B and C subunit 1 AS18 Novel putative protease (ORF1 novel 7 antigen like) A S19 Novelautolysin 6 A S20 Novel surface protein/toxin 13 A S21 γhemolysin B andC subunit 1 A S25 γhemolysin B and C subunit 1 A S29 Fibrinogen bindingprotein) 3 A S44 Novel surface protein 12 A S45 Atl 2 A S55 Atl 2 A S64Atl 2 A S66 Atl 2 B 2 Novel exotoxin (exotoxin 2 like) 8 C 1 Coagulase 4C 2 Coagulase 4 C 3 Coagulase 4 C 4 Coagulase 4 C 5 Coagulase 4 C 6Coagulase 4 C 7 Coagulase 4 C 8 Coagulase 4 C 9 Coagulase 4 C 10Coagulase 4 C 11 Coagulase 4 C 13 Coagulase 4 C 14 Coagulase 4 C 15Coagulase 4 C 19 Coagulase 4 C 20 Coagulase 4 C 25 Coagulase 4 E 6 Novelsurface proteins 9/10 E 7 Novel surface proteins 9/10 E 11 γhemolysin Band C subunit 1 F 1 Novel exotoxin (exotoxin 2 like) 8 F 2 Novelexotoxin (exotoxin 2 like) 8 F 3 Novel exotoxin (exotoxin 2 like) 8 F 4Novel exotoxin (exotoxin 2 like) 8 F 5 Novel hemolysin (YjfD) 11

[0105]

1 32 1 2260 DNA Staphylococcus aureus 1 gatcttaatg aaagagtgac tgatgccttagcaattgcta gttgtatcaa tgcgcatccg 60 tatgtcaaag gagaactttg cgtgtccgatgacttaacgt atacgacagg ttattttgcc 120 gctgctaaaa ttggttacca tcgattatttgatattaaac cagttaatac gagatatgga 180 ggcagaataa tatttgtgga cgattgtattgatttaaatc attacatatc atttttagaa 240 agcacaccga agcaagttgt ttatgaaacggtataggggt tttagtatga catcaaaaga 300 tattactcaa attagtgtca ttgctgcgattttaaccatt ttggcagttt tgaaaatacc 360 gtccattata ccaggattag attttcaattatctgcaccg gcagcattat tgatattagc 420 tttctttgga attaaaaagt actttttaggtggattatta tctagcctat tattactagt 480 atttggcgta tttaatccaa ttaatgtgattatctctatt atatttagag ttatagctat 540 tgcagttgtt tatttattga aaataaatgtactatcatta gttttagcaa gtgtattagg 600 cagtttggta tataggctac tattatctattattttaaat ttacctgtgt gggtagtgtt 660 gttaaacgcg attccaggcg taatattcactttaattgta gctattcctt tatatctcac 720 attgagaaaa agaatggcag tattactaagataataaatc aaaacacggt cgtcacaatt 780 actgttggcg accgtgtttt actagctatttattgttttc agtttctttt gtatctaaca 840 atttcacttt gtgattttcc caatcaatttcatatgttga tttaaatgtt ctagttttaa 900 agtttttata atttgcgcct gcccagtagaagccattcca acgaatttgg tataaatcca 960 tttcacgttg ataagttact gtaattttagattttttagc gccatcttgt ctgtgtgata 1020 gtacgcttaa aaattctgga ttgaagttacttctagataa taatggcatt tggtgttgcg 1080 ctatgaagtt ttggccagcg tatgcactgctttgtctgcc agctaagaag agttcattac 1140 catatgttgg gtggaagcta tctcttccataaggtcccca accattattc ataattttat 1200 gtgcttcaac tccccagcca acatttttataatttgtgtt gcgacttaat gttgttctgt 1260 aactttcttg tttataatta attgtttcagaaaaagctgt atttccatta agtccaccag 1320 ataaaccatt agagatacta atgtcaccaccaaatgtata gcctaaagta ttttgaactt 1380 gaaactcttc attttgattt tttggtgcataatcaacgac gtttactgaa tcattagatt 1440 gtgagcttat agatacattg tatttagctccccaatataa ttttgaaaag tcatagtcat 1500 taggattagg tttcacaaag cctgagttaatattcccagt agctttaagt actaaagtat 1560 ctttatcata acttttatct ttgatgaaattaaatgttaa aatctgtgaa attttaaatt 1620 tatcagaatc tgctgtggct gttgttttgtataaagtaac tttgtcatcg acttttttta 1680 cgctgactgg tgttatttta ccttcagcattagcagtacc agaaagtaat aataatgcca 1740 tagatgtagc aacggatgat ttgactaatttattcatttt catatcaatt ctgtcctttc 1800 accttgattt catgagtctt ccaattgacctcgtatttca cagtatagtt tctatttaca 1860 aatgcattat ggactctatg tccgtctaaataactgttgc cataatgcgt tgatctttta 1920 atggcatgag tgacatccat gtttcttccgtaagtaattt caaattcgct tgtatcgctt 1980 gaaccttttt catgagatac tgtggcgataaatgaagggt taaatccact ttgtacaaga 2040 ggtggtaact cactgtctgg aacgaaataatctctaggat ctttactatg aggtttgtag 2100 cctacaaata aatcgctatc aaaggctgatttttgacctg attcagtggc gaatgaattc 2160 gctttgacgc cccataaaac actttttgagttttgttgtt ctacttcact tacataattt 2220 tgttgtgtat agctaatcga tttagaatagttaaatgatc 2260 2 2902 DNA Staphylococcus aureus 2 gatcgtataa tcgaaacagcaccaacggat tacttatctt ggggtgtcgg tgcagtcggt 60 aaccctagat tcatcaatgttgaaatcgta cacacacacg actatgcttc atttgcacgt 120 tcaatgaata actatgctgactatgcagct acacaattac aatattatgg tttaaaacca 180 gacagtgctg agtatgatggaaatggtaca gtatggactc actacgctgt aagtaaatat 240 ttaggtggta ctgaccatgccgatccacat ggatatttaa gaagtcataa ttatagttat 300 gatcaattat atgacttaattaatgaaaaa tatttaataa aaatgggtaa agtggcgcca 360 tggggtacgc aatctacaactacccctact acaccatcaa aaccaacaac accgtcgaaa 420 ccatcaactg gtaaattaacagttgctgca aacaatggtg tcgcacaaat caaaccaaca 480 aatagtggtt tatatactactgtatacgac aaaactggta aagcaactaa tgaagttcaa 540 aaaacatttg ctgtatctaaaacagctaca ttaggtaatc aaaaattcta tcttgttcaa 600 gattacaatt ctggtaataaatttggttgg gttaaagaag gcgatgtggt ttacaacaca 660 gctaaatcac ctgtaaatgtaaatcaatca tattcaatca aacctggtac gaaactttat 720 acagtacctt ggggtacatctaaacaagtt gctggtagtg tgtctggctc tggaaaccaa 780 acatttaagg cttcaaagcaacaacaaatt gataaatcaa tttatttata tggctctgtg 840 aatggtaaat ctggttgggtaagtaaagca tatttagttg atactgctaa acctacgcct 900 acaccaacac ctaagccatcaacacctaca acaaataata aattaacagt ttcatcatta 960 aacggtgttg ctcaaattaatgctaaaaac aatggcttat tcactacagt ttatgacaaa 1020 actggtaagc caacgaaagaagttcaaaaa acatttgctg taacaaaaga agcaagttta 1080 ggtggaaaca aattctacttagttaaagat tacaatagtc caactttaat tggttgggtt 1140 aaacaaggtg acgttatttataacaatgca aaatcacctg taaatgtaat gcaaacatat 1200 acagtaaaac caggcactaaattatattca gtaccttggg gcacttataa acaagaagct 1260 ggtgcagttt ctggtacaggtaaccaaact tttaaagcga ctaagcaaca acaaattgat 1320 aaatctatct atttatttggaactgtaaat ggtaaatctg gttgggtaag taaagcatat 1380 ttagctgtac ctgctgcacctaaaaaagca gtagcacaac caaaaacagc tgtaaaagct 1440 tatactgtta ctaaaccacaaacgactcaa acagttagca agattgctca agttaaacca 1500 aacaacactg gtattcgtgcttctgtttat gaaaaaacag cgaaaaacgg tgcgaaatat 1560 gcagaccgta cgttctatgtaacaaaagag cgtgctcatg gtaatgaaac gtatgtatta 1620 ttaaacaata caagccataacatcccatta ggttggttca atgtaaaaga cttaaatgtt 1680 caaaacttag gcaaagaagttaaaacgact caaaaatata ctgttaataa atcaaataac 1740 ggcttatcaa tggttccttggggtactaaa aaccaagtca ttttaacagg caataacatt 1800 gctcaaggta catttaatgcaacgaaacaa gtatctgtag gcaaagatgt ttatttatac 1860 ggtactatta ataaccgcactggttgggta aatgcaaaag atttaactgc accaactgct 1920 gtgaaaccaa ctacatcagctgccaaagat tataactaca cttatgtaat taaaaatggt 1980 aatggttatt actatgtaacaccaaattct gatacagcta aatactcatt aaaagcattt 2040 aatgaacaac cattcgcagttgttaaagaa caagtcatta atggacaaac ttggtactat 2100 ggtaaattat ctaacggtaaattagcatgg attaaatcaa ctgatttagc taaagaatta 2160 attaagtata atcaaacaggtatggcatta aaccaagttg ctcaaataca agctggttta 2220 caatataaac cacaagtacaacgtgtacca ggtaagtgga caggtgctaa ctttaatgat 2280 gttaagcatg caatggatacgaagcgttta gctcaagatc cagcattaaa atatcaattc 2340 ttacgcttag accaaccacaaaatatttct attgataaaa ttaatcaatt cttaaaaggt 2400 aaaggtgtat tagaaaaccaaggtgctgca tttaacaaag ctgctcaaat gtatggcatt 2460 aatgaagttt atcttatctcacatgcccta ttagaaacag gtaacggtac ttctcaatta 2520 gcgaaaggtg cagatgtagtgaacaacaaa gttgtaacta actcaaacac gaaataccat 2580 aacgtatttg gtattgctgcatatgataac gatcctttac gtgaaggtat taaatatgct 2640 aaacaagctg gttgggacacagtatcaaaa gcaatcgttg gtggtgctaa attcatcggc 2700 aactcatatg taaaagctggtcaaaataca ctttacaaaa tgagatggaa tcctgcacat 2760 ccaggaacac accaatatgctacagatgta gattgggcta acatcaatgc taaaatcatc 2820 aaaggctact atgataaaattggcgaagtc ggcaaatact tcgacatccc acaatataaa 2880 taagcaacat gaacataggatc 2902 3 2792 DNA Staphylococcus aureus 3 gatcaactta atataatgaattcggcaaca gaagagcatc atcataaaga ttatattaaa 60 ctatataatt taggtggcggtgctgctaaa aaaattgcaa tagaggtttt attggggaag 120 gataaagtca ttcagaaaaaatacgtgcat attttaccta gtaaagaagg gtacatgtta 180 ccaattaata aaaatgtgtacgaagaatta gaaagaacga ttgagaacaa tggtcatgaa 240 gctgatttga atgtacgtatgacttattat cataatgtaa gtcgcaaaca acaggaagtt 300 atattaaaag gtcaaatcgaccgttttaat acttataata ataaagaaat ttatgatttg 360 cagtttatct aaaaattgatttaagagggt agttgtttat tgcgaaaaat atcattcaat 420 tttaatgaaa taatggcgtcattactataa aatattactt tatgttgtaa tgcatttttc 480 tataagatag aactaaaaggaggggcaaag atgcaaatta gacaaataca tcaacatgac 540 tttgctcaag tggaccagttaattagaacg gcatttgaaa atagtgaaca tggttatggt 600 aatgaatcag agctagtagaccaaattcgt ctaagtgata cgtatgacaa taccttagaa 660 ttagtagctg ttcttcaaaatgaagttgta gggcacggtt tactaagtga agtttatctt 720 gataacgagg cacaacgggaaattggatta gtgttagcac ctgtatctgt tgatattcat 780 catcaaaata aaggtattgggaagcgattg attcaagcat tagaacgaga agcaatatta 840 aaaggatata attttatcagtgtattagga tggccgacgt attatgccaa tctaggatat 900 caacgcgcaa gtatgtacgacatttatcca ccatatgatg gtataccaga cgaagcgttt 960 ttaattaaag aattaaaagtgaacagttta gcgggaaaaa caggtaccat aaattacaca 1020 tctgcttttg aaaaaatatgatttcaagct aggattacat taggtagagt tcatattaat 1080 aataaaaaat gtttgcaatcaaatcgtacg ttgtcgtttg taattcttaa aatagcaata 1140 aataaaatgt ttgttagtaaagtattattg tggataataa aatatcgata caaattaatt 1200 gctataatgc aattttagtgtataattcca ttaacagaga ttaaatatat ctttaaaggg 1260 tatatagtta atataaaatgactttttaaa aagagggaat aaaatgaata tgaagaaaaa 1320 agaaaaacac gcaattcggaaaaaatcgat tggcgtggct tcagtgcttg taggtacgtt 1380 aatcggtttt ggactactcagcagtaaaga agcagatgca agtgaaaata gtgttacgca 1440 atctgatagc gcaagtaacgaaagcaaaag taatgattca agtagcgtta gtgctgcacc 1500 taaaacagac gacacaaacgtgagtgatac taaaacatcg tcaaacacta ataatggcga 1560 aacgagtgtg gcgcaaaatccagcacaaca ggaaacgaca caatcatcat caacaaatgc 1620 aactacggaa gaaacgccggtaactggtga agctactact acgacaacga atcaagctaa 1680 tacaccggca acaactcaatcaagcaatac aaatgcggag gaattagtga atcaaacaag 1740 taatgaaacg acttctaatgatactaatac agtatcatct gtaaattcac ctcaaaattc 1800 tacaaatgcg gaaaatgtttcaacaacgca agatacttca actgaagcaa caccttcaaa 1860 caatgaatca gctccacagagtacagatgc aagtaataaa gatgtagtta atcaagcggt 1920 taatacaagt gcgcctagaatgagagcatt tagtttagcg gcagtagctg cagatgcacc 1980 ggcagctggc acagatattacgaatcagtt gacgaatgtg acagttggta ttgactctgg 2040 tacgactgtg tatccgcaccaagcaggtta tgtcaaactg aattatggtt tttcagtgcc 2100 taattctgct gttaaaggtgacacattcaa aataactgta cctaaagaat taaacttaaa 2160 tggtgtaact tcaactgctaaagtgccacc aattatggct ggagatcaag tattggcaaa 2220 tggtgtaatc gatagtgatggtaatgttat ttatacattt acagactatg taaatactaa 2280 agatgatgta aaagcaactttgaccatgcc cgcttatatt gaccctgaaa atgttaaaaa 2340 gacaggtaat gtgacattggctactggcat aggtagtaca acagcaaaca aaacagtatt 2400 agtagattat gaaaaatatggtaagtttta taacttatct attaaaggta caattgacca 2460 aatcgataaa acaaataatacgtatcgtca gacaatttat gtcaatccaa gtggagataa 2520 cgttattgcg ccggttttaacaggtaattt aaaaccaaat acggatagta atgcattaat 2580 agatcagcaa aatacaagtattaaagtata taaagtagat aatgcagctg atttatctga 2640 aagttacttt gtgaatccagaaaactttga ggatgtcact aatagtgtga atattacatt 2700 cccaaatcca aatcaatataaagtagagtt taatacgcct gatgatcaaa ttacaacacc 2760 gtatatagta gttgttaatggtcatattga tc 2792 4 2478 DNA Staphylococcus aureus 4 gatcgaattgaacgaagcat ttgcttctca aacgattgca tctattaaag aagtaggtct 60 agatatatcacgtacgaatg tgaatggtgg cgctattgct ttaggtcatc cattaggtgc 120 tacaggcgcaatgttaaccg cgcgtttact taatgaaatg ggtagacgtc ccgatagccg 180 ttacggcatggttacgatgt gtattggtgt cggcatgggt gcagctgcta tatttgaata 240 tgtgcgttagaatggttgat tttggatgaa gcggattcgt tttgttattg aatgaagtag 300 gctgaagttgaagccagttg aagttgaagc gggttgaagc aatttcgttt tattaatgaa 360 gctgtgtgaaatatagtgat tgaacaaaaa agtggtttaa tgggatggtg gttatttccg 420 ttttagaatttaacatttac acgtctaatt ttaatcattg ttttaaattt tatgaatcga 480 agccctttgatttaataata tttgctaatg ctagtaactt atctgattgt tcatgtttaa 540 aataaagaaaaccactcaca tcagtgtgtg ttcgaactag acttgtaagt tccagttcgg 600 cacgactttctaaagcaatt attattgctg tgattgtcgt atatcactta gatgtgcgtg 660 gtttattttaataggttagt aatatattag gtcatgttat gtttaagact ataatgaata 720 aataatttagaaatatgctt ccgattgttc gatgctttaa ttcagttaga agcatcatag 780 aatgcatgattactgttgta aagatacgta atgttttgta ttgactgtat gtctttggat 840 agagttacaaacttattttg ttactctagg cccatatgtc gcagtaccat ctgcatgtgt 900 tgttacattgtatgcatttg ttttacttgg cttcttgtat gtcgggcgag ctccgtatga 960 cacttgaccgtttgcatgtg ttgttacgtt gtatgcattt gttttgcttg gcttgttttg 1020 tgttgggcgagcgccatatg atacttggcc gtttccatgt gttgttacgt tatatgcgtt 1080 tgttttgcttggcttgtttt gtgtcggacg agctccgtat gatacttggc cgtttgcatg 1140 tgttgttacattgtatgcat tcgtttcgct tggcttcttg tatgtcggac gagctccgta 1200 tgatacttgaccatttgcat gtgttgttac gttatatgca tttgtttctg atggcttatt 1260 gaatcttggtctcgcttcat atccaaatgt tccatcgttg tattcacgga tacctgtacc 1320 agcatctctatatttaacat atttaggtgt tttgttaaat tgcggtctcg gaccatattg 1380 agaagcttctgttgtttcag ttgcttgagg tttaacttca atatcacttg attctccttg 1440 agtaccttttaacgttgatt cagtaccttg tggttttatt tcaagtttag atgagctacc 1500 ttcaagaccttctaaaatag ggttcgttaa cggtgggttt gtataattat tgcttaatga 1560 tgggccgctttgttccattg ttagaaaatc gggaccttga acgatttcac cttgtaccgt 1620 tttattttccatcgttggat attccggacc ttttacaatt tcacctgtaa ttgtgccctg 1680 tggaattttaactaatggtt gtgcaactgg ttgtgttgtt tcttcagctt taccagccgt 1740 agttttaacctcttgttggt tatcaacttt aggtgcttga ggttcttcaa ctttcttctc 1800 ttcttttactactggcgatt ttgtttcagt ttctccgtat tttttgacag ttttcttttt 1860 ccaagaatcatctgcttctt taactgcttt tttcgtttct tcaactaatt tatcaaaatt 1920 aggtttattatcactatttg ttttatagtt atgtgttgta ggattatatt tcgttataga 1980 tttcggtctattttgtttag tttccataaa gaaatcatca ataattgaat ttaagtcatc 2040 aatcatttcttttttaatac gttcatttgt aattttatgt ggattgtctg tatctccaag 2100 gattaagtccagttttgctc gtaactcttt cgcgtgctcc ccataatcct tatcaccata 2160 atatgatacaactaatgtat caatttcaga tacgagatcg tatacttcct tagttgcttt 2220 atcttcttctgctgcattaa aagttttcaa gtctgaattc ttatccttaa tatctttaac 2280 ttctctgtgaaaatcatcca gtgctctctt taatgcatcc tgtagttcat tgtattcttt 2340 catcgaaagttcttctaaat tatatttatg aaaattagcc atttttaaat ctgtacgagg 2400 attttcttttttataatttg cataccattg tttataatct tcatattgag atttctttct 2460 ctccaaaagatattgatc 2478 5 2070 DNA Staphylococcus aureus 5 tgacgctgct tttgtaaatacatataattt ttccacttca tgatttaatt cgttcgcatg 60 atctttgtaa tttctaccaaaagcaatcac attattcgga ggtgttactg gtggtaaaaa 120 ttcaatgtca ttaaatgaaattttatagtc ttcagctttg ccgctatctt ctgctgctac 180 aactgcttta cgtacttgttcttgaaaatc taaagtatga ttttgttgta aaccagctaa 240 caatgtttta ggatggaaatctccttctgc aaagtcagca aatacttgtg ttaaatccca 300 tacagcatct tcgcgttttactttaacgcc atatgaagtt ttgtcattat acttgaatga 360 taagaatttc attcattctcaactcctcgt ctttatctta attcacatta taactttttt 420 cgttatcaaa taacaaataaataagtaaga caattttgaa aatgagttgt gttcattctg 480 ctacaaggac tttgcacttaatcgaaatta ttttttattc ttttgaaaat caaaatacta 540 tagttgcaat gtaccaaatttgaagaagta taaataacct ttaacttctt tattaagaat 600 cgtttgaagc gtattttgataatatttcat ctgtatctta tatttatttt ttaattgtgt 660 accaatttct tcatctgtcatcccacggcg acgattaaat gcatcggttt tatagtctac 720 aaaataatgc acaccatctttaacaaagat taagtcaatc ataccttgaa taattgagac 780 gtcttcgtct ccttgtggcaattggtcaac taatgcttgg ttaactacaa acggtaattc 840 acgataaact tgctctgcttcagcaataat cgaatataac tcactattga taaatgtcat 900 tatttcatcc atacggatatcttttttcgc atctgcttcg ataatatgtt tatcgattaa 960 tccatcgata tactgatgtaactcaacttc agatatgcgt tcttttttga atggtaaatg 1020 ttgcatcact gtatgcattaacgtaccaat ttcattcgct tttcgtttac cttgttcact 1080 tagaaattta ggtcgttcatacgttgaaaa accgatacga tattgcctta ctcgttcgta 1140 acttgtgcca ctttcttctgtttcatattg tcttttcaat tcagaaacag attgttttga 1200 gggcttttta gtatcatttacatatggata tcgataatca agttggtgtt taatttgtgc 1260 tttaacatct tcattaccattttgcatagt ttctaattga ttaaccgaac gatattcatc 1320 attatctaaa atggtttctgtagacacatc ttcaaagtac acaattgaaa tatttacatt 1380 cggacgacta ctatcttcaatttgtgctat atctttttca aattttaaat catctggaat 1440 tgacgcagat tgatgtttagataaaatact ataaataaga tggaacggat ttggtgaagt 1500 taatcgttca ttgacagcaatgtgctcacc agaaatagac aattgctcta gttctagtaa 1560 tgatttatca tttttcactctaccaattaa ataaagttgt tctttcgctc ttgttaatgc 1620 tacatagact aatcgcatttcttctgacac aagttctttt tcggcaacag ctctatatgc 1680 aaccgaagct aaagatggaaatgccatttc tttatccaca tcaaaataat ccattccgag 1740 accaaattgc tgatttaaaataactggttg tttcaaatca cgtttattaa aatcttttga 1800 caatccagaa taaatgacaaatggaaactc tagaccttta ctactatgaa ttgtcatcat 1860 tctaacgaca ttatcgtttggaccaactac attttcctca ccaaaatctt tgcctctttc 1920 aatcaattca tcgataaaacgaataaattg atataaacct ctaaaacttg aattctcaaa 1980 ctcgatagct ttattaaataaaccataaag atttgcacgt cgtccacgtc caccaataag 2040 tccactaaag tattgaataacataatgatc 2070 6 2394 DNA Staphylococcus aureus 6 gatcagattt attagacagtattccagata tacccacacc aaagccagaa aagacgttaa 60 cacttggtaa aggtaatggattgttaagtg gattattaaa tgctgatggt aatgtatctt 120 tgcctaaagc gggggaaacgataaaagaac attggttgcc gatatctgta attgttggtg 180 caatgggtgt actaatgatttggttatcac gacgcaataa gttgaaaaat aaagcataat 240 tatattgggg gaagagcatctatatatttt tttaagtata taagacgtct tatttcccct 300 taatttattg tgaagtatatgcaaaatgca atgaatagat tgtccatcat tttaacgtta 360 taatgaattt aacgacttagaactacacaa gtaaaggaga atgaagatgt ctcgaaaaac 420 ggcgctatta gttttggatatgcaagaagg tatagcgagt agtgtaccta gaataaaaaa 480 tattattaaa gcgaatcagagagcaattga agcagcaaga caacatcgaa taccagtcat 540 tttcatacgt ttagtgttagataagcattt taatgatgtc tcctcgagta ataaagtgtt 600 ttcaacaatt aaagctcaaggatatgcgat tactgaagca gatgcatcta cacgaatact 660 tgaagattta gcaccactagaagatgagcc gattatttct aagcgacgct ttagcgcatt 720 tacaggtagt tacttggaagtttatttacg tgcaaatgat attaatcatt tagtattaac 780 gggtgtctct acaagtggagctgtattgag cacggcatta gaaagtgtag ataaagacta 840 ttatattact gttttagaagatgctgttgg tgatagatca gatgataaac atgactttat 900 tattgaacaa attttatcacgctcatgtga cattgaatcc gtagagtcat ggaaaagtag 960 tttatagtta atataacgtcaattaaagct cggcagtaat gtttgagaat aagtacattt 1020 gctcatattt ataaaatgtgtgagatggca attgaaacgg atatgatgag gaacatttga 1080 acataaaata atatatttatataaaacgac ccgaggcgtt cgaactgaat gcctcgggtt 1140 taattgaata agaaatcggacttatgaaca gaaatatgtt taagtccgaa ctccttgttt 1200 atacttataa attttacgggtttaatataa tacttattta cctgtaatat atgataattc 1260 ttcagcggca gctgcgttgatagttctatg agaaatgata cctaatcctt taacattgga 1320 ttctgaaata acgatagaaccatcactgtt aactttttca acaaatgcta catgaccgta 1380 atgttgatct gcaccaaattgtccagcctc aaatacaaca gcagcatgac gttttggtgt 1440 atgacttact tgataatcacggtattgagc tcgattattc caattatgtg catcacctaa 1500 atcacctgag atagatgtaccaaattgttt catacggtta tatacgtacc aagtacattg 1560 gccatgtgga tatggcatactatcagatac ctcacggaaa ggtttgaatt catctgatga 1620 atcatcataa tccttgatagaacgttcata tttatctaaa tctggcatgc gttcatcgtc 1680 aaactgagtt aattgatagtgtttaataat actgtttaat ttcttagcat agtttggatc 1740 tgtagcatat gttttagataagtgtgatgt tgcatcttta taagaatcgg cttccgattt 1800 ccatgttggt ttataaattgttcgattgcc atcaatacca tttttaataa ggtcagagta 1860 atcttttagt gattctttcgtgcttggata ttttcggaat ccagcattaa tactatacaa 1920 ttgattacca tcagcttctaatgtgttaaa aggaacagaa ttcccttcaa aagcaccttt 1980 gataccgaat aaattatggtttggtgactt agctaaagca ctacgacctg agtcagattc 2040 taagattgct tgggcaatcatgacagacgc ataaatatcg ttatcttgac caatgcgatg 2100 tgcatcttta gcaattgatttgacaaattg acgtgtatct tttgagtcaa caacgttaaa 2160 ttgtccgcta tcatcattgttagatatact aggatctgtt tcgaataatg atgttgcacg 2220 tgtatccttt tgattaacatcgttattgaa tgattgagca ggtttagatt tatgtttcaa 2280 ttcatcttgt gttggtaactgtggattctt tgtattagat ttttcatttt tgtctttttt 2340 agattgagat gcataatctttttgtgtttt ctttgcatct tcactgtatt gatc 2394 7 2033 DNA Staphylococcusaureus 7 gatctggaac aggtttcatt gtcggtaaaa atacaattgt taccaacaagcatgtcgttg 60 caggtatgga aattggtgca catattatag cgcatcccaa tggtgaatataataatggcg 120 gattttataa agttaaaaaa attgtccgtt attcaggtca agaagatattgccattctac 180 atgtggaaga taaagctgtt catccaaaaa acaggaattt taaagattacacaggcattt 240 taaaaatagc atcagaagct aaagaaaatg aacgcatttc aattgttggctatccagaac 300 catatataaa taaatttcaa atgtatgagt caacaggaaa agtgctgtcagttaaaggca 360 acatgattat tactgatgct ttcgtagaac caggcaactc aggttcagctgtatttaaca 420 gtaaatacga agttgtaggt gttcactttg gtggaaacgg ccctggaaataaaagtacaa 480 aaggatatgg tgtttatttc tctcctgaaa ttaagaaatt cattgcagataacacagata 540 aataaatcct tacatagata aatgatttta aaaattaaca acaaactcaacaattcaaat 600 catctctgtg attccattta ttcgaaatga ttaaaaaaaa taaaacttcaaaaagctaac 660 attataatta tacaaatact tagaggagca gaaaaatgaa taaaaatataatcatcaaaa 720 gtattgcagc attgacgatt ttaacatcaa taactggtgt cggcacaacaatggttgaag 780 gtattcaaca aacagccaaa gccgaaaata ctgttaaaca aattacaaatacaaatgttg 840 caccatacag tggtgttaca tggatgggcg ctggaacagg atttgtagttggaaatcata 900 caatcattac caataaacat gttacctatc acatgaaagt cggtgatgaaatcaaagcac 960 atcctaatgg tttttataat aacggtggtg gactttataa agttactaagattgtagatt 1020 atcctggtaa agaagatatt gcggttgtac aagttgaaga aaaatcaacacaaccaaaag 1080 gtagaaaatt caaagatttc actagtaaat ttaatatagc atcagaagctaaagaaaatg 1140 aacctatatc agtcattggt tatccaaatc ctaatggaaa taaactacaaatgtatgaat 1200 caactggtaa agtattatca gtgaatggga atatagtgtc ttcggatgcaattattcagc 1260 ctggtagctc tggttcacct atattaaata gtaaacacga agctattggtgtaatctatg 1320 ccggtaataa gccatcaggt gaaagcacaa gaggatttgc tgtttatttctctcctgaaa 1380 ttaagaaatt cattgcagat aatttagata aataattaaa acttagacattcacccaatc 1440 ctgacaaaat atactataac taacatttat taatatatat tgcattatttaatatgcatc 1500 aaagccaatc aacgattgat tttcaccaac tcaattgttg attggttttatttatgtatg 1560 aatgaacaac tttttgacat cattaagaat ataaatgatt ttgaaagcatttgaaagcta 1620 caacatttct ataaaatttt tcaataacaa ttgcgccact aaaactcaaaatttccacca 1680 ccaacatcca aattatcaac atcgcaacat aaccaaatgt tataataaatctattacaca 1740 aagagataaa ttacttatgc aaaggcggag gaatcacatg tctattactgaaaaacaacg 1800 tcagcaacaa gctgaattac ataaaaaatt atggtcgatt gcgaatgatttaagagggaa 1860 catggatgcg agtgaattcc gtaattacat tttaggcttg attttctatcgcttcttatc 1920 tgaaaaagcc gaacaagaat atgcagatgc cttgtcaggt gaagacatcacgtatcaaga 1980 agcatgggca gatgaagaat atcgtgaaga cttaaaagca gaattaattgatc 2033 8 2794 DNA Staphylococcus aureus 8 gatcaaacgt tgcttaacttctttttaatg cttaaaaatt atttcaaagg cacatagaaa 60 cgctatatta atctcatactcactcattat tttttgctta aattacttaa taatacttca 120 ataattgtta aaaggggtttaatgtgatta tcttagaacg ccatctataa tgatgttgta 180 tgattcaaat tacgtaaaaagacaatcgaa tataatatag attggagcat acaattatga 240 aaatgagaac aattgctaaaaccagtttag cactagggct tttaacaaca ggcgcaatta 300 cagtaacgac gcaatcggtcaaagcagaaa aaatacaatc aactaaagtt gacaaagtac 360 caacgcttaa agcagagcgattagcaatga taaacataac agcaggtgca aattcagcga 420 caacacaagc agctaacacaagacaagaac gcacgcctaa actcgaaaag gcaccaaata 480 ctaatgagga aaaaacctcagcttccaaaa tagaaaaaat atcacaacct aaacaagaag 540 agcagaaaac gcttaatatatcagcaacgc cagcgcctaa acaagaacaa tcacaaacga 600 caaccgaatc cacaacgccgaaaactaaag tgacaacacc tccatcaaca aacacgccac 660 aaccaatgca atctactaaatcagacacac cacaatctcc aaccataaaa caagcacaaa 720 cagatatgac tcctaaatatgaagatttaa gagcgtatta tacaaaaccg agttttgaat 780 ttgaaaagca gtttggatttatgctcaaac catggacgac ggttaggttt atgaatgtta 840 ttccaaatag gttcatctataaaatagctt tagttggaaa agatgagaaa aaatataaag 900 atggacctta cgataatatcgatgtattta tcgttttaga agacaataaa tatcaattga 960 aaaaatattc tgtcggtggcatcacgaaga ctaatagtaa aaaagttaat cacaaagtag 1020 aattaagcat tactaaaaaagataatcaag gtatgatttc acgcgatgtt tcagaataca 1080 tgattactaa ggaagagatttccttgaaag agcttgattt taaattgaga aaacaactta 1140 ttgaaaaaca taatctttacggtaacatgg gttcaggaac aatcgttatt aaaatgaaaa 1200 acggtgggaa atatacgtttgaattacaca aaaaactgca agagcatcgt atggcagacg 1260 tcatagatgg cactaatattgataacattg aagtgaatat aaaataatca tgacattctc 1320 taaatagaag ctgtcatcggaaaaacaaga agttaagtga caacggttta catgttgctt 1380 agcttctttt attatgcgtaatgatgtaaa aagacgaata ttcatttgtt tgtaaaagtg 1440 gcatttctat gtcttaaaagtgacgaaact tcaaatgtgc caagtgttga atcacatcaa 1500 aatcattttt atttaacgaacattatggat ttcttaattt acttaacgat gattcaaata 1560 tagttaaaca aggtttaatgtgaatggagc aatacgccat ctataataaa gctgtatgat 1620 tcaatgaatg taatcgaacaaatctaataa ttacgaatgg agcatacaac tatgaaaata 1680 acaacgattg ctaaaacaagtttagcacta ggccttttaa caacaggtgt aatcacaacg 1740 acaacgcaag cagcaaacgcgacaacacta tcttccacta aagtggaagc accacaatca 1800 acaccgccct caactaaaatagaagcaccg caatcaaaac caaacgcgac aacaccgccc 1860 tcaactaaag tagaagcaccgcaacaaaca gcaaatgcga caacaccgcc ttcaactaaa 1920 gtgacaacac ctccatcaacaaacacgcca caaccaatgc aatctactaa atcagacaca 1980 ccacaatcgc caaccacaaaacaagtacca acagaaataa atcctaaatt taaagattta 2040 agagcgtatt atacgaaaccaagtttagaa tttaaaaatg agattggtat tattttaaaa 2100 aaatggacga caataagatttatgaatgtt gtcccagatt atttcatata taaaattgct 2160 ttagttggta aagatgataaaaaatatggt gaaggagtac ataggaatgt cgatgtattt 2220 gtcgttttag aagaaaataattacaatctg gaaaaatatt ctgtcggtgg tatcacaaag 2280 agtaatagta aaaaagttgatcacaaagca ggagtaagaa ttactaagga agataataaa 2340 ggtacaatct ctcatgatgtttcagaattc aagattacta aagaacagat ttccttgaaa 2400 gaacttgatt ttaaattgagaaaacaactt attgaaaaaa ataatctgta cggtaacgtt 2460 ggttcaggta aaattgttattaaaatgaaa aacggtggaa agtacacgtt tgaattgcac 2520 aaaaaattac aagaaaatcgcatggcagat gtcatagatg gcactaatat tgataacatt 2580 gaagtgaata taaaataatcatgacattct ctaaatagaa gctgtcatcg gaaaaacaag 2640 aagttaagtg acaacggcctacatgttgct tagcttcttt tgttatgttc gatgatttga 2700 gaacccgaat tttcgatgggtccaaatatg acgtggaaga gacctgaatt tatctgtaaa 2760 tccctatcta tcgggtgtgaagcacaacgg gatc 2794 9 505 DNA Staphylococcus aureus 9 gatcatagcgcaccaaactc tcgtccaatt gattttgaaa tgaaaaagaa agatggaact 60 caacagttttatcattatgc aagttctgtt aaacctgcta gagttatttt cactgattca 120 aaaccagaaattgaattagg attacaatca ggtcaatttt ggagaaaatt tgaagtttat 180 gaaggtgacaaaaagttgcc aattaaatta gtatcatacg atactgttaa agattatgct 240 tacattcgcttctctgtatc aaacggaaca aaagctgtta aaattgttag ttcaacacac 300 ttcaataacaaagaagaaaa atacgattac acattaatgg aattcgcaca accaatttat 360 aacagtgcagataaattcaa aactgaagaa gattataaag ctgaaaaatt attagcgcca 420 tataaaaaagcgaaaacact agaaagacaa gtttatgaat taaataaaat tcaagataaa 480 cttcctgaaaaattaaaggc tgagt 505 10 673 DNA Staphylococcus aureus 10 gatcaaactaaaacacaaac tgctcataca gttaaaacag cacaaactgc tcaagaacaa 60 aataaagttcaaacacctgt taaagatgtt gcaacagcga aatctgaaag caacaatcaa 120 gctgtaagtgataataaatc acaacaaact aacaaagtta caaaacataa cgaaacgcct 180 aaacaagcatctaaagctaa agaattacca aaaactggtt taacttcagt tgataacttt 240 attagcacagttgccttcgc aacacttgcc cttttaggtt cattatcttt attacttttc 300 aaaagaaaagaatctaaata aatcatcgtc acactcataa cttaatatat tttttatttt 360 aaattttatttaacctatgt catagatatt tcataatcta taacataggt tatttttttt 420 ataaaataacgttgcaatta actaacattt caatgtcaat acaagtaatc aattgataat 480 gattatcagttgataatata caattaggag ttgtttctac aacatgaaca aacagcaaaa 540 agaatttaaatcattttatt caattagaaa gtcatcacta ggcgtgcatc tgtagcaatt 600 agtacacttttattattaat gtcaaatggc gaagcacaag ccagcagctt gaagaaaaca 660 ggtggtccaattc 673 11 2238 DNA Staphylococcus aureus 11 gatcttcagc ttgatgttttcgtttgatta aattggtaaa atagaaacgc aatccacaaa 60 aatggcaagc actaaaataatgtttggggg tgcttgtgct tttgtggatt gcggtcgatt 120 atttatattg catgatttgattaatttgat tgattatatt ggacatgatg gtgttggcgg 180 gatgcgttgt tgctagtcgcgggctttgtc cactccacat atgtattaac tctttgtcgc 240 cgatgtttgc tgcggcttttcttatgctac ttgttagctc attttgtatt ggataatctg 300 ggatatcgcc ttcgtattgggacatttctt cgataaacct attgttgata ccgcgtgcaa 360 gctttccact aaacgcttttgtaatgactg tatctgtttc tttactattt ataattgcat 420 ctcgcagtag ttctgatgcattactgtctt gtgatgttaa aaatgcggtg cccatttgta 480 ccccttctgc acctaagacaatacttgcca aaactcctct accatccata attccaccag 540 cggcaatgac cggaattgaaacgacatcta caatttgtgg cactaaagat attgttccaa 600 ccataggtaa ttgatttttaggttttaaaa atgaaccacg atgtccacct gcttcactac 660 cttgagcaac gatagcatccatacccgctt tttcattcgc aatagcttca tcaacacttg 720 ttgctgtacc tataagtttgacattcgctg ctttcaacct gcttataatc tgttcgcttg 780 gaattccaaa agtaaaacaacatacaggca cttgcttttt aattatcgta tcaatatgac 840 acttaaattg ttgttcttcggtaattttta caaccggctc ttctaaatgt aatgcgcgtc 900 gataaggttt taaccatgcattcatatttt caatttgact actggtatat gattgttgac 960 ttggtacaaa gacatttacgccaaaagaat ttgacgttaa ttggcgtaca taatctattt 1020 catcttccaa ttgctgcgtattaaagtaac ctgcgcctat tgtgcctaac ccaccactgt 1080 tacttactga tgcaactaatttcggtgtcg tacttcctgc catacctgct tgtataattg 1140 gatattcaat acttaacatttgagtaagtc gattcttatt ccacatagct gttcgctcct 1200 tatatagata cgttgcgatttttccgttgt tgaaattgaa tttgctgttg agaaagtttt 1260 tctttttcct ttttatccatctcatcttca atttccatac ctaataattc ttcaattaag 1320 tcttcatgtg acactatcgcttcagtacca ccaaattcgt ccaacacaat tgctaaatgt 1380 tttctagaaa tagtcatcttacgtaatacc cattcagctt tattgtgttc attcacaaat 1440 aatggcttag ctgaatagtttgtaatttga ttttcttttt tattactcca agccaacaga 1500 tatttagaat gaaacaccccaataatgtta tcaatatctc cctcgtacac tggatatcta 1560 gtgtatggct tattcataaccgtttcataa acttcttcgt atgtcgcatt tgaagcaaat 1620 gccgtcacat taattctaggtgttgtatct acatctttta cttttaaatt ttcaaaatta 1680 atgacacctt ccaacctactcgtctcaatt tcatttaaag caccttcatg tccagcaatt 1740 gctaacattg ttttaaattcttcttttgaa aattgatgtt cttgaggttg gcccttagat 1800 aaacttcgat taatactgtccgtcaactta tttaaaagta atgtgatagg acggaacaca 1860 atgacacaaa tattaataattggatataca agccttgtta ttttatctgg aaatgttgca 1920 gcgacagact tgggaatcacttcggagatc aaaatgataa caactgttaa aacagctgat 1980 gcaataccaa cgctaatcccccaacgtaaa gccataattg taacaagtgt tggtaataaa 2040 atattcgcga cattattcccaattagaatc gttgtaataa actcacttgg tttttcaagt 2100 aactttacaa tgccttttgcttttttatca cctttgtcag cttcagtttt aaattttgct 2160 ttattggcag ccgttaatgccgtctcgctt cctgaaaaga aaaacgaaat aaatatcaat 2220 ataattatgg caatgatc2238 12 7975 DNA Staphylococcus aureus 12 gatcaaacga caattattaattcgttaacg tttactgaaa cagtaccaaa tagaagttat 60 gcaagagcaa gtgcgaatgaaatcactagt aaaacagtta gtaatgtcag tcgtactgga 120 aataatgcca atgtcacagtaactgttact tatcaagatg gaacaacatc aacagtgact 180 gtacctgtaa agcatgtcattccagaaatc gttgcacatt cgcattacac tgtacaaggc 240 caagacttcc cagcaggtaatggttctagt gcatcagatt actttaagtt atctaatggt 300 agtgacattg cagatgcaactattacatgg gtaagtggac aagcgccaaa taaagataat 360 acacgtattg gtgaagatataactgtaact gcacatatct taattgatgg cgaaacaacg 420 ccgattacga aaacagcaacatataaagta gtaagaactg taccgaaaca tgtctttgaa 480 acagccagag gtgttttatacccaggtgtt tcagatatgt atgatgcgaa acaatatgtt 540 aagccagtaa ataattcttggtcgacaaat gcgcaacata tgaatttcca atttgttgga 600 acatatggtc ctaacaaagatgttgtaggc atatctactc gtcttattag agtgacatat 660 gataatagac aaacagaagatttaactatt ttatctaaag ttaaacctga cccacctaga 720 attgacgcaa actctgtgacatataaagca ggtcttacaa accaagaaat taaagttaat 780 aacgtattaa ataactcgtcagtaaaatta tttaaagcag ataatacacc attaaatgtc 840 acaaatatta ctcatggtagcggttttagt tcggttgtga cagtaagtga cgcgttacca 900 aatggcggaa ttaaagcaaaatcttcaatt tcaatgaaca atgtgacgta tacgacgcaa 960 gacgaacatg gtcaagttgttacagtaaca agaaatgaat ctgttgattc aaatgacagt 1020 gcaacagtaa cagtgacaccacaattacaa gcaactactg aaggcgctgt atttattaaa 1080 ggtggcgacg gttttgatttcggacacgta gaaagattta ttcaaaaccc gccacatggg 1140 gcaacggttg catggcatgatagtccagat acatggaaga atacagtcgg taacactcat 1200 aaaactgcgg ttgtaacattacctaatggt caaggtacgc gtaatgttga agttccagtc 1260 aaagtttatc cagttgctaatgcaaaggcg ccatcacgtg atgtgaaagg tcaaaatttg 1320 actaatggaa cggatgcgatgaactacatt acatttgatc caaatacaaa cacaaatggt 1380 atcactgcag catgggcaaatagacaacaa ccaaataacc aacaagcagg cgtgcaacat 1440 ttaaatgtcg atgtcacatatccaggtatt tcagctgcta aacgagttcc tgttactgtt 1500 aatgtatatc aatttgaattccctcaaact acttatacga caacggttgg aggcacttta 1560 gcaagtggta cgcaagcatcaggatatgca catatgcaaa atgctactgg tttaccaaca 1620 gatggattta cgtataaatggaatcgtgat actacaggta caaatgacgc aaactggtca 1680 gctatgaata aaccgaatgtggctaaagtc gttaacgcaa aatatgacgt catctataac 1740 ggacatactt ttgcaacatctttaccagcg aaatttgtag taaaagatgt gcaaccagcg 1800 aaaccaactg tgactgaaacagcggcagga gcgattacaa ttgcacctgg agcaaaccaa 1860 acagtgaata cacatgccggtaacgtaacg acatacgctg ataaattagt tattaaacgt 1920 aatggtaacg ttgtgacgacatttacacgt cgcaataata cgagtccatg ggtgaaagaa 1980 gcatctgcag caactgtagcaggtattgct ggaactaata atggtattac tgttgcagca 2040 ggtactttca accctgctgatacaattcaa gttgttgcaa cgcaaggaag cggagagaca 2100 gtgagtgatg agcaacgtagtgatgatttc acagttgtcg caccacaacc gaaccaagcg 2160 actactaaga tttggcaaaatggtcatatt gatatcacgc ctaataatcc atcaggacat 2220 ttaattaatc caactcaagcaatggatatt gcttacactg aaaaagtggg taatggtgca 2280 gaacatagta agacaattaatgttgttcgt ggtcaaaata atcaatggac aattgcgaat 2340 aagcctgact atgtaacgttagatgcacaa actggtaaag tgacgttcaa tgccaatact 2400 ataaaaccaa attcatcaatcacaattact ccgaaagcag gtacaggtca ctcagtaagt 2460 agtaatccaa gtacattaactgcaccggca gctcatactg tcaacacaac tgaaattgtg 2520 aaagattatg gttcaaatgtaacagcagct gaaattaaca atgcagttca agttgctaat 2580 aaacgtactg caacgattaaaaatggcaca gcaatgccta ctaatttagc tggtggtagc 2640 acaacgacga ttcctgtgacagtaacttac aatgatggta gtactgaaga agtacaagag 2700 tccattttca caaaagcggataaacgtgag ttaatcacag ctaaaaatca tttagatgat 2760 ccagtaagca ctgaaggtaaaaagccaggt acaattacgc agtacaataa tgcaatgcat 2820 aatgcgcaac aacaaatcaatactgcgaaa acagaagcac aacaagtgat taataatgag 2880 cgtgcaacac cacaacaagtttctgacgca ctaactaaag ttcgtgcagc acaaactaag 2940 attgatcaag ctaaagcattacttcaaaat aaagaagata atagccaatt agtaacgtct 3000 aaaaataact tacaaagttctgtgaaccaa gtaccatcaa ctgctggtat gacgcaacaa 3060 agtattgata actataatgcgaagaagcgt gaagcagaaa ctgaaataac tgcagctcaa 3120 cgtgttattg acaatggcgatgcaactgca caacaaattt cagatgaaaa acatcgtgtc 3180 gataacgcat taacagcattaaaccaagcg aaacatgatt taactgcaga tacacatgcc 3240 ttagagcaag cagtgcaacaattgaatcgc acaggtacaa cgactggtaa gaagccggca 3300 agtattactg cttacaataattcgattcgt gcacttcaaa gtgacttaac aagtgctaaa 3360 aatagcgcta atgctattattcaaaagcca ataagaacag tacaagaagt gcaatctgcg 3420 ttaacaaatg taaatcgtgtcaatgagcga ttaacgcaag caattaatca attagtacct 3480 ttagctgata atagtgctttaaaaactgct aagacgaaac ttgatgaaga aatcaataaa 3540 tcagtaacta ctgatggtatgacacaatca tcaatccaag catatgaaaa tgctaaacgt 3600 gcgggtcaaa cagaatcaacaaatgcacaa aatgttatta acaatggtga tgcgactgac 3660 caacaaattg ccgcagaaaaaacaaaagta gaagaaaaat ataatagctt aaaacaagca 3720 attgctggat taactccagacttggcacca ttacaaactg caaaaactca gttgcaaaat 3780 gatattgatc agccaacgagtacgactggt atgacaagcg catctattgc agcatttaat 3840 gaaaaacttt cagcagctagaactaaaatt caagaaattg atcgtgtatt agcctcacat 3900 ccagatgttg cgacaatacgtcaaaacgtg acagcagcga atgccgctaa atcagcactt 3960 gatcaagcac gtaatggcttaacagtcgat aaagcgcctt tagaaaatgc gaaaaatcaa 4020 ctacaatata gtattgacacgcaaacaagt acaactggta tgacacaaga ctctataaat 4080 gcatacaatg cgaagttaacagctgcacgt aataagattc aacaaatcaa tcaagtatta 4140 gcaggttcac cgactgtagaacaaattaat acaaatacgt ctacagcaaa tcaagctaaa 4200 tctgatttag atcatgcacgtcaagcttta acaccagata aagcgccgct tcaaactgcg 4260 aaaacgcaat tagaacaaagcattaatcaa ccaacggata caacaggtat gacgaccgct 4320 tcgttaaatg cgtacaaccaaaaattacaa gcagcgcgtc aaaagttaac tgaaattaat 4380 caagtgttga atggcaacccaactgtccaa aatatcaatg ataaagtgac agaggcaaac 4440 caagctaagg atcaattaaatacagcacgt caaggtttaa cattagatag acagccagcg 4500 ttaacaacat tacatggtgcatctaactta aaccaagcac aacaaaataa tttcacgcaa 4560 caaattaatg ctgctcaaaatcatgctgcg cttgaaacaa ttaagtctaa cattacggct 4620 ttaaatactg cgatgacgaaattaaaagac agtgttgcgg ataataatac aattaaatca 4680 gatcaaaatt acactgacgcaacaccagct aataaacaag cgtatgataa tgcagttaat 4740 gcggctaaag gtgtcattggagaaacgact aatccaacga tggatgttaa cacagtgaac 4800 caaaaagcag catctgttaaatcgacgaaa gatgctttag atggtcaaca aaacttacaa 4860 cgtgcgaaaa cagaagcaacaaatgcgatt acgcatgcaa gtgatttaaa ccaagcacaa 4920 aagaatgcat taacacaacaagtgaatagt gcacaaaacg tgcaagcagt aaatgatatt 4980 aaacaaacga ctcaaagcttaaatactgct atgacaggtt taaaacgtgg cgttgctaat 5040 cataaccaag tcgtacaaagtgataattat gtcaacgcag atactaataa gaaaaatgat 5100 tacaacaatg catacaaccatgcgaatgac attattaatg gtaatgcaca acatccagtt 5160 ataacaccaa gtgatgttaacaatgcttta tcaaatgtca caagtaaaga acatgcattg 5220 aatggtgaag ctaagttaaatgctgcgaaa caagaagcga atactgcatt aggtcattta 5280 aacaatttaa ataatgcacaacgtcaaaac ttacaatcgc aaattaatgg tgcgcatcaa 5340 attgatgcag ttaatacaattaagcaaaat gcaacaaact tgaatagtgc aatgggtaac 5400 ttaagacaag ctgttgcagataaagatcaa gtgaaacgta cagaagatta tgcggatgca 5460 gatacagcta aacaaaatgcatataacagt gcagtttcaa gtgccgaaac aatcattaat 5520 caaacaacaa atccaacgatgtctgttgat gatgttaatc gtgcaacttc agctgttact 5580 tctaataaaa atgcattaaatggttatgaa aaattagcac aatctaaaac agatgctgca 5640 agagcaattg atgcattaccacatttaaat aatgcacaaa aagcagatgt taaatctaaa 5700 attaatgctg catcaaatattgctggcgta aatactgtta aacaacaagg tacagattta 5760 aatacagcga tgggtaacttgcaaggtgca atcaatgatg aacaaacgac gcttaatagt 5820 caaaactatc aagatgcgacacctagtaag aaaacagcat acacaaatgc ggtacaagct 5880 gcgaaagata ttttaaataaatcaaatggt caaaataaaa cgaaagatca agttactgaa 5940 gcgatgaatc aagtgaattctgctaaaaat aacttagatg gtacgcgttt attagatcaa 6000 gcgaagcaaa cagcaaaacagcagttaaat aatatgacgc atttaacaac tgcacaaaaa 6060 acgaatttaa caaaccaaattaatagtggt actactgtcg ctggtgttca aacggttcaa 6120 tcaaatgcca atacattagatcaagccatg aatacgttaa gacaaagtat tgccaacaaa 6180 gatgcgacta aagcaagtgaagattacgta gatgctaata atgataagca aacagcatat 6240 aacaacgcag tagctgctgctgaaacgatt attaatgcta atagtaatcc agaaatgaat 6300 ccaagtacga ttacacaaaaagcagagcaa gtgaatagtt ctaaaacggc acttaacggt 6360 gatgaaaact tagctgctgcaaaacaaaat gcgaaaacgt acttaaacac attgacaagt 6420 attacagatg ctcaaaagaacaatttgatt agtcaaatta ctagtgcgac aagagtgagt 6480 ggtgttgata ctgtaaaacaaaatgcgcaa catctagacc aagctatggc tagcttacag 6540 aatggtatta acaacgaatctcaagtgaaa tcatctgaga aatatcgtga tgctgataca 6600 aataaacaac aagagtatgataatgctatt actgcagcga aagcgatttt aaataaatcg 6660 acaggtccaa acactgcgcaaaatgcagtt gaagcagcat tacaacgtgt taataatgcg 6720 aaagatgcat tgaatggtgatgcaaaatta attgcagctc aaaacgcagc gaaacaacat 6780 ttaggtactt taacgcatatcactacagct caacgtaatg atttaacaaa tcaaatttca 6840 caagctacaa acttagctggtgttgaatct gttaaacaaa atgcgaatag tttagatggt 6900 gctatgggta acttacaaacggctatcaac gataagtcag gaacattagc gagccaaaac 6960 ttcttggatg ctgatgagcaaaaacgtaat gcatacaatc aagctgtatc agcagccgaa 7020 accattttaa ataaacaaactggaccgaat acagcgaaaa cagcagtcga acaagcactt 7080 aataatgtta ataatgcgaaacatgcatta aatggtacgc aaaacttaaa caatgcgaaa 7140 caagcagcga ttacagcaatcaatggcgca tctgatttaa atcaaaaaca aaaagatgca 7200 ttaaaagcac aagctaatggtgctcaacgc gtatctaatg cacaagatgt acagcacaat 7260 gcgactgaac tgaacacggcaatgggcaca ttaaaacatg ccatcgcaga taagacgaat 7320 acgttagcaa gcagtaaatatgttaatgcc gatagcacta aacaaaatgc ttacacaact 7380 aaagttacca atgctgaacatattattagc ggtacgccaa cggttgttac gacaccttca 7440 gaagtaacag ctgcagctaatcaagtaaac agcgcgaaac aagaattaaa tggtgacgaa 7500 agattacgtg aagcaaaacaaaacgccaat actgctattg atgcattaac acaattaaat 7560 acacctcaaa aagctaaattaaaagaacaa gtgggacaag ccaatagatt agaagacgta 7620 caaactgttc aaacaaatggacaagcattg aacaatgcaa tgaaaggctt aagagatagt 7680 attgctaacg aaacaacagtcaaaacaagt caaaactata cagacgcaag tccgaataac 7740 caatcaacat ataatagcgctgtgtcaaat gcgaaaggta tcattaatca aactaacaat 7800 ccgactatgg atactagtgcgattacccaa gctacaacac aagtgaataa tgctaaaaat 7860 ggtttaaacg gtgctgaaaacttaagaaat gcacaaaaca ctgctaagca aaacttaaat 7920 acattatcac acttaacaaataaccaaaaa tctgccatct catcacaaat tgatc 7975 13 2001 DNA Staphylococcusaureus 13 gatcatggca ttgtatttaa tgcaagtcta cctttgtaca aagatgccatccatcaaaaa 60 ggatcaatgc gcagtaatga caatggtgat gatatgagta tgatggtgggtacagtgctg 120 agtggctttg aatatcgagc gcaaaaagaa aagtatgata acttatataaattcttcaaa 180 gaaaatgaaa agaaatatca atatacaggc tttacaaaag aggcaattaacaagacacaa 240 aatgtcggat ataaaaatga atatttttat attacatact cttctagaagtttaaaagaa 300 tatcgaaagt attatgaacc actgattcga aaaaatgata aagaatttaaagaaggaatg 360 gaacgagcaa gaaaagaagt gaattacgct gcaaatacag atgctgttgctacacttttt 420 tctactaaga aaaactttac taaagacaat acagtagatg atgtaatcgaactaagtgat 480 aaattatata atttaaaaaa taaaccagat aaatctacaa tcacaatacaaatagggaaa 540 cccactatta atactaagaa agccttttat gatgataatc gtccaatagaatatggggtg 600 cacagtaaag atgaataaaa ttaatgatag ggatttaaca gaattaagtagttactgggt 660 ttatcaaaat attgatataa aaaaagaatt taaagttaat ggaaaaaggtttaaacaagt 720 agacagttat aatgatgata agaatagtaa tttgaatggt gctgctgatattaaaatata 780 tgagttatta gatgataaaa gtaaaccaac tggtcaacag acaataatttatcaaggaac 840 atctaatgag gcaattaatc caaataatcc attaaaatca tcggggtttggagatgattg 900 gctccaaaat gctaaattaa tgaataatga taatgaaagc acagattatttaaagcaaac 960 agatcaatta tcaaatcaat ataaaataaa gttagaagat gcagatagattatcaaatag 1020 tgatttttta aaaaaatata gaatggaatc aagtaacttc aaaaacaaaaccattgtggc 1080 ggatggcggt aattcggaag gcggtgcagg agcaaaatat caaggagcgaaacatccgaa 1140 tgaaaaagtt gttgctactg actcagcaat gattccttat gctgcttggcagaaatttgc 1200 tagaccacgc tttgataata tgattagttt taatagtacc aacgatttattaacatggtt 1260 acaagatcca ttcatcaaag atatgccagg aaaacgcgtt aacattaatgatggtgtgcc 1320 caggttagat actttaatag acagccatgt aggttataaa aggaagttaaatagaaaaga 1380 taacacatac gatactgtac cactaatcaa aataaagtcg gtaaaagatacagaaattaa 1440 aaatggaaaa aaagtaaaaa agactattaa cataacatta gatatggatgggcgaattcc 1500 aataaatgtt tggacaggag attcgattgc acgttctgga agaggaactttaattaaact 1560 taatttagaa aatcttgatg cgttgagtaa actgattact ggtgaaacaagtggtatgtt 1620 agcagaatgc gtaatctttt taaatgaaag ttttaacatc tcagaaaatgaaaataaaaa 1680 ttttgcagat agaaagaaac aattatcaga aggatttaag gataagattaacttatttca 1740 gttagaagaa atggaaagaa ctttaattag taaaataaac tcacttgaagaagttgcaga 1800 tgaaacaata gaaagtatta gtgctgttaa acacttatta cctgattttgcattggatgc 1860 attaaaagaa agaattaatg agttgtttaa aggtataaaa tcttttatagaaaaagtgta 1920 tgatagtata gataatgaaa ttttagaaat tttcaaaaat atagatcacgacttcagaga 1980 tggagtatct gaagaaatga t 2001 14 106 PRT Staphylococcusaureus 14 Asp Gln Thr Lys Thr Gln Thr Ala His Thr Val Lys Thr Ala GlnThr 1 5 10 15 Ala Gln Glu Gln Asn Lys Val Gln Thr Pro Val Lys Asp ValAla Thr 20 25 30 Ala Lys Ser Glu Ser Asn Asn Gln Ala Val Ser Asp Asn LysSer Gln 35 40 45 Gln Thr Asn Lys Val Thr Lys His Asn Glu Thr Pro Lys GlnAla Ser 50 55 60 Lys Ala Lys Glu Leu Pro Lys Thr Gly Leu Thr Ser Val AspAsn Phe 65 70 75 80 Ile Ser Thr Val Ala Phe Ala Thr Leu Ala Leu Leu GlySer Leu Ser 85 90 95 Leu Leu Leu Phe Lys Arg Lys Glu Ser Lys 100 105 15960 PRT Staphylococcus aureus 15 Asp Arg Ile Ile Glu Thr Ala Pro Thr AspTyr Leu Ser Trp Gly Val 1 5 10 15 Gly Ala Val Gly Asn Pro Arg Phe IleAsn Val Glu Ile Val His Thr 20 25 30 His Asp Tyr Ala Ser Phe Ala Arg SerMet Asn Asn Tyr Ala Asp Tyr 35 40 45 Ala Ala Thr Gln Leu Gln Tyr Tyr GlyLeu Lys Pro Asp Ser Ala Glu 50 55 60 Tyr Asp Gly Asn Gly Thr Val Trp ThrHis Tyr Ala Val Ser Lys Tyr 65 70 75 80 Leu Gly Gly Thr Asp His Ala AspPro His Gly Tyr Leu Arg Ser His 85 90 95 Asn Tyr Ser Tyr Asp Gln Leu TyrAsp Leu Ile Asn Glu Lys Tyr Leu 100 105 110 Ile Lys Met Gly Lys Val AlaPro Trp Gly Thr Gln Ser Thr Thr Thr 115 120 125 Pro Thr Thr Pro Ser LysPro Thr Thr Pro Ser Lys Pro Ser Thr Gly 130 135 140 Lys Leu Thr Val AlaAla Asn Asn Gly Val Ala Gln Ile Lys Pro Thr 145 150 155 160 Asn Ser GlyLeu Tyr Thr Thr Val Tyr Asp Lys Thr Gly Lys Ala Thr 165 170 175 Asn GluVal Gln Lys Thr Phe Ala Val Ser Lys Thr Ala Thr Leu Gly 180 185 190 AsnGln Lys Phe Tyr Leu Val Gln Asp Tyr Asn Ser Gly Asn Lys Phe 195 200 205Gly Trp Val Lys Glu Gly Asp Val Val Tyr Asn Thr Ala Lys Ser Pro 210 215220 Val Asn Val Asn Gln Ser Tyr Ser Ile Lys Pro Gly Thr Lys Leu Tyr 225230 235 240 Thr Val Pro Trp Gly Thr Ser Lys Gln Val Ala Gly Ser Val SerGly 245 250 255 Ser Gly Asn Gln Thr Phe Lys Ala Ser Lys Gln Gln Gln IleAsp Lys 260 265 270 Ser Ile Tyr Leu Tyr Gly Ser Val Asn Gly Lys Ser GlyTrp Val Ser 275 280 285 Lys Ala Tyr Leu Val Asp Thr Ala Lys Pro Thr ProThr Pro Thr Pro 290 295 300 Lys Pro Ser Thr Pro Thr Thr Asn Asn Lys LeuThr Val Ser Ser Leu 305 310 315 320 Asn Gly Val Ala Gln Ile Asn Ala LysAsn Asn Gly Leu Phe Thr Thr 325 330 335 Val Tyr Asp Lys Thr Gly Lys ProThr Lys Glu Val Gln Lys Thr Phe 340 345 350 Ala Val Thr Lys Glu Ala SerLeu Gly Gly Asn Lys Phe Tyr Leu Val 355 360 365 Lys Asp Tyr Asn Ser ProThr Leu Ile Gly Trp Val Lys Gln Gly Asp 370 375 380 Val Ile Tyr Asn AsnAla Lys Ser Pro Val Asn Val Met Gln Thr Tyr 385 390 395 400 Thr Val LysPro Gly Thr Lys Leu Tyr Ser Val Pro Trp Gly Thr Tyr 405 410 415 Lys GlnGlu Ala Gly Ala Val Ser Gly Thr Gly Asn Gln Thr Phe Lys 420 425 430 AlaThr Lys Gln Gln Gln Ile Asp Lys Ser Ile Tyr Leu Phe Gly Thr 435 440 445Val Asn Gly Lys Ser Gly Trp Val Ser Lys Ala Tyr Leu Ala Val Pro 450 455460 Ala Ala Pro Lys Lys Ala Val Ala Gln Pro Lys Thr Ala Val Lys Ala 465470 475 480 Tyr Thr Val Thr Lys Pro Gln Thr Thr Gln Thr Val Ser Lys IleAla 485 490 495 Gln Val Lys Pro Asn Asn Thr Gly Ile Arg Ala Ser Val TyrGlu Lys 500 505 510 Thr Ala Lys Asn Gly Ala Lys Tyr Ala Asp Arg Thr PheTyr Val Thr 515 520 525 Lys Glu Arg Ala His Gly Asn Glu Thr Tyr Val LeuLeu Asn Asn Thr 530 535 540 Ser His Asn Ile Pro Leu Gly Trp Phe Asn ValLys Asp Leu Asn Val 545 550 555 560 Gln Asn Leu Gly Lys Glu Val Lys ThrThr Gln Lys Tyr Thr Val Asn 565 570 575 Lys Ser Asn Asn Gly Leu Ser MetVal Pro Trp Gly Thr Lys Asn Gln 580 585 590 Val Ile Leu Thr Gly Asn AsnIle Ala Gln Gly Thr Phe Asn Ala Thr 595 600 605 Lys Gln Val Ser Val GlyLys Asp Val Tyr Leu Tyr Gly Thr Ile Asn 610 615 620 Asn Arg Thr Gly TrpVal Asn Ala Lys Asp Leu Thr Ala Pro Thr Ala 625 630 635 640 Val Lys ProThr Thr Ser Ala Ala Lys Asp Tyr Asn Tyr Thr Tyr Val 645 650 655 Ile LysAsn Gly Asn Gly Tyr Tyr Tyr Val Thr Pro Asn Ser Asp Thr 660 665 670 AlaLys Tyr Ser Leu Lys Ala Phe Asn Glu Gln Pro Phe Ala Val Val 675 680 685Lys Glu Gln Val Ile Asn Gly Gln Thr Trp Tyr Tyr Gly Lys Leu Ser 690 695700 Asn Gly Lys Leu Ala Trp Ile Lys Ser Thr Asp Leu Ala Lys Glu Leu 705710 715 720 Ile Lys Tyr Asn Gln Thr Gly Met Ala Leu Asn Gln Val Ala GlnIle 725 730 735 Gln Ala Gly Leu Gln Tyr Lys Pro Gln Val Gln Arg Val ProGly Lys 740 745 750 Trp Thr Gly Ala Asn Phe Asn Asp Val Lys His Ala MetAsp Thr Lys 755 760 765 Arg Leu Ala Gln Asp Pro Ala Leu Lys Tyr Gln PheLeu Arg Leu Asp 770 775 780 Gln Pro Gln Asn Ile Ser Ile Asp Lys Ile AsnGln Phe Leu Lys Gly 785 790 795 800 Lys Gly Val Leu Glu Asn Gln Gly AlaAla Phe Asn Lys Ala Ala Gln 805 810 815 Met Tyr Gly Ile Asn Glu Val TyrLeu Ile Ser His Ala Leu Leu Glu 820 825 830 Thr Gly Asn Gly Thr Ser GlnLeu Ala Lys Gly Ala Asp Val Val Asn 835 840 845 Asn Lys Val Val Thr AsnSer Asn Thr Lys Tyr His Asn Val Phe Gly 850 855 860 Ile Ala Ala Tyr AspAsn Asp Pro Leu Arg Glu Gly Ile Lys Tyr Ala 865 870 875 880 Lys Gln AlaGly Trp Asp Thr Val Ser Lys Ala Ile Val Gly Gly Ala 885 890 895 Lys PheIle Gly Asn Ser Tyr Val Lys Ala Gly Gln Asn Thr Leu Tyr 900 905 910 LysMet Arg Trp Asn Pro Ala His Pro Gly Thr His Gln Tyr Ala Thr 915 920 925Asp Val Asp Trp Ala Asn Ile Asn Ala Lys Ile Ile Lys Gly Tyr Tyr 930 935940 Asp Lys Ile Gly Glu Val Gly Lys Tyr Phe Asp Ile Pro Gln Tyr Lys 945950 955 960 16 386 PRT Staphylococcus aureus 16 Asp Gln Tyr Ser Glu AspAla Lys Lys Thr Gln Lys Asp Tyr Ala Ser 1 5 10 15 Gln Ser Lys Lys AspLys Asn Glu Lys Ser Asn Thr Lys Asn Pro Gln 20 25 30 Leu Pro Thr Gln AspGlu Leu Lys His Lys Ser Lys Pro Ala Gln Ser 35 40 45 Phe Asn Asn Asp ValAsn Gln Lys Asp Thr Arg Ala Thr Ser Leu Phe 50 55 60 Glu Thr Asp Pro SerIle Ser Asn Asn Asp Asp Ser Gly Gln Phe Asn 65 70 75 80 Val Val Asp SerLys Asp Thr Arg Gln Phe Val Lys Ser Ile Ala Lys 85 90 95 Asp Ala His ArgIle Gly Gln Asp Asn Asp Ile Tyr Ala Ser Val Met 100 105 110 Ile Ala GlnAla Ile Leu Glu Ser Asp Ser Gly Arg Ser Ala Leu Ala 115 120 125 Lys SerPro Asn His Asn Leu Phe Gly Ile Lys Gly Ala Phe Glu Gly 130 135 140 AsnSer Val Pro Phe Asn Thr Leu Glu Ala Asp Gly Asn Gln Leu Tyr 145 150 155160 Ser Ile Asn Ala Gly Phe Arg Lys Tyr Pro Ser Thr Lys Glu Ser Leu 165170 175 Lys Asp Tyr Ser Asp Leu Ile Lys Asn Gly Ile Asp Gly Asn Arg Thr180 185 190 Ile Tyr Lys Pro Thr Trp Lys Ser Glu Ala Asp Ser Tyr Lys AspAla 195 200 205 Thr Ser His Leu Ser Lys Thr Tyr Ala Thr Asp Pro Asn TyrAla Lys 210 215 220 Lys Leu Asn Ser Ile Ile Lys His Tyr Gln Leu Thr GlnPhe Asp Asp 225 230 235 240 Glu Arg Met Pro Asp Leu Asp Lys Tyr Glu ArgSer Ile Lys Asp Tyr 245 250 255 Asp Asp Ser Ser Asp Glu Phe Lys Pro PheArg Glu Val Ser Asp Ser 260 265 270 Met Pro Tyr Pro His Gly Gln Cys ThrTrp Tyr Val Tyr Asn Arg Met 275 280 285 Lys Gln Phe Gly Thr Ser Ile SerGly Asp Leu Gly Asp Ala His Asn 290 295 300 Trp Asn Asn Arg Ala Gln TyrArg Asp Tyr Gln Val Ser His Thr Pro 305 310 315 320 Lys Arg His Ala AlaVal Val Phe Glu Ala Gly Gln Phe Gly Ala Asp 325 330 335 Gln His Tyr GlyHis Val Ala Phe Val Glu Lys Val Asn Ser Asp Gly 340 345 350 Ser Ile ValIle Ser Glu Ser Asn Val Lys Gly Leu Gly Ile Ile Ser 355 360 365 His ArgThr Ile Asn Ala Ala Ala Ala Glu Glu Leu Ser Tyr Ile Thr 370 375 380 GlyLys 385 17 325 PRT Staphylococcus aureus 17 Met Lys Met Asn Lys Leu ValLys Ser Ser Val Ala Thr Ser Met Ala 1 5 10 15 Leu Leu Leu Leu Ser GlyThr Ala Asn Ala Glu Gly Lys Ile Thr Pro 20 25 30 Val Ser Val Lys Lys ValAsp Asp Lys Val Thr Leu Tyr Lys Thr Thr 35 40 45 Ala Thr Ala Asp Ser AspLys Phe Lys Ile Ser Gln Ile Leu Thr Phe 50 55 60 Asn Phe Ile Lys Asp LysSer Tyr Asp Lys Asp Thr Leu Val Leu Lys 65 70 75 80 Ala Thr Gly Asn IleAsn Ser Gly Phe Val Lys Pro Asn Pro Asn Asp 85 90 95 Tyr Asp Phe Ser LysLeu Tyr Trp Gly Ala Lys Tyr Asn Val Ser Ile 100 105 110 Ser Ser Gln SerAsn Asp Ser Val Asn Val Val Asp Tyr Ala Pro Lys 115 120 125 Asn Gln AsnGlu Glu Phe Gln Val Gln Asn Thr Leu Gly Tyr Thr Phe 130 135 140 Gly GlyAsp Ile Ser Ile Ser Asn Gly Leu Ser Gly Gly Leu Asn Gly 145 150 155 160Asn Thr Ala Phe Ser Glu Thr Ile Asn Tyr Lys Gln Glu Ser Tyr Arg 165 170175 Thr Thr Leu Ser Arg Asn Thr Asn Tyr Lys Asn Val Gly Trp Gly Val 180185 190 Glu Ala His Lys Ile Met Asn Asn Gly Trp Gly Pro Tyr Gly Arg Asp195 200 205 Ser Phe His Pro Thr Tyr Gly Asn Glu Leu Phe Leu Ala Gly ArgGln 210 215 220 Ser Ser Ala Tyr Ala Gly Gln Asn Phe Ile Ala Gln His GlnMet Pro 225 230 235 240 Leu Leu Ser Arg Ser Asn Phe Asn Pro Glu Phe LeuSer Val Leu Ser 245 250 255 His Arg Gln Asp Gly Ala Lys Lys Ser Lys IleThr Val Thr Tyr Gln 260 265 270 Arg Glu Met Asp Leu Tyr Gln Ile Arg TrpAsn Gly Phe Tyr Trp Ala 275 280 285 Gly Ala Asn Tyr Lys Asn Phe Lys ThrArg Thr Phe Lys Ser Thr Tyr 290 295 300 Glu Ile Asp Trp Glu Asn His LysVal Lys Leu Leu Asp Thr Lys Glu 305 310 315 320 Thr Glu Asn Asn Lys 32518 157 PRT Staphylococcus aureus 18 Ser Phe Asn Tyr Ser Lys Ser Ile SerTyr Thr Gln Gln Asn Tyr Val 1 5 10 15 Ser Glu Val Glu Gln Gln Asn SerLys Ser Val Leu Trp Gly Val Lys 20 25 30 Ala Asn Ser Phe Ala Thr Glu SerGly Gln Lys Ser Ala Phe Asp Ser 35 40 45 Asp Leu Phe Val Gly Tyr Lys ProHis Ser Lys Asp Pro Arg Asp Tyr 50 55 60 Phe Val Pro Asp Ser Glu Leu ProPro Leu Val Gln Ser Gly Phe Asn 65 70 75 80 Pro Ser Phe Ile Ala Thr ValSer His Glu Lys Gly Ser Ser Asp Thr 85 90 95 Ser Glu Phe Glu Ile Thr TyrGly Arg Asn Met Asp Val Thr His Ala 100 105 110 Ile Lys Arg Ser Thr HisTyr Gly Asn Ser Tyr Leu Asp Gly His Arg 115 120 125 Val His Asn Ala PheVal Asn Arg Asn Tyr Thr Val Lys Tyr Glu Val 130 135 140 Asn Trp Lys ThrHis Glu Ile Lys Val Lys Gly Gln Asn 145 150 155 19 345 PRTStaphylococcus aureus 19 Ile Ile Ala Ile Ile Ile Leu Ile Phe Ile Ser PhePhe Phe Ser Gly 1 5 10 15 Ser Glu Thr Ala Leu Thr Ala Ala Asn Lys AlaLys Phe Lys Thr Glu 20 25 30 Ala Asp Lys Gly Asp Lys Lys Ala Lys Gly IleVal Lys Leu Leu Glu 35 40 45 Lys Pro Ser Glu Phe Ile Thr Thr Ile Leu IleGly Asn Asn Val Ala 50 55 60 Asn Ile Leu Leu Pro Thr Leu Val Thr Ile MetAla Leu Arg Trp Gly 65 70 75 80 Ile Ser Val Gly Ile Ala Ser Ala Val LeuThr Val Val Ile Ile Leu 85 90 95 Ile Ser Glu Val Ile Pro Lys Ser Val AlaAla Thr Phe Pro Asp Lys 100 105 110 Ile Thr Arg Leu Val Tyr Pro Ile IleAsn Ile Cys Val Ile Val Phe 115 120 125 Arg Pro Ile Thr Leu Leu Leu AsnLys Leu Thr Asp Ser Ile Asn Arg 130 135 140 Ser Leu Ser Lys Gly Gln ProGln Glu His Gln Phe Ser Lys Glu Glu 145 150 155 160 Phe Lys Thr Met LeuAla Ile Ala Gly His Glu Gly Ala Leu Asn Glu 165 170 175 Ile Glu Thr SerArg Leu Glu Gly Val Ile Asn Phe Glu Asn Leu Lys 180 185 190 Val Lys AspVal Asp Thr Thr Pro Arg Ile Asn Val Thr Ala Phe Ala 195 200 205 Ser AsnAla Thr Tyr Glu Glu Val Tyr Glu Thr Val Met Asn Lys Pro 210 215 220 TyrThr Arg Tyr Pro Val Tyr Glu Gly Asp Ile Asp Asn Ile Ile Gly 225 230 235240 Val Phe His Ser Lys Tyr Leu Leu Ala Trp Ser Asn Lys Lys Glu Asn 245250 255 Gln Ile Thr Asn Tyr Ser Ala Lys Pro Leu Phe Val Asn Glu His Asn260 265 270 Lys Ala Glu Trp Val Leu Arg Lys Met Thr Ile Ser Arg Lys HisLeu 275 280 285 Ala Ile Val Leu Asp Glu Phe Gly Gly Thr Glu Ala Ile ValSer His 290 295 300 Glu Asp Leu Ile Glu Glu Leu Leu Gly Met Glu Ile GluAsp Glu Met 305 310 315 320 Asp Lys Lys Glu Lys Glu Lys Leu Ser Gln GlnGln Ile Gln Phe Gln 325 330 335 Gln Arg Lys Asn Arg Asn Val Ser Ile 340345 20 133 PRT Staphylococcus aureus 20 Met Asn Lys Gln Gln Lys Glu PheLys Ser Phe Tyr Ser Ile Arg Lys 1 5 10 15 Ser Ser Leu Gly Val Ala SerVal Ala Ile Ser Thr Leu Leu Leu Leu 20 25 30 Met Ser Asn Gly Glu Ala GlnAla Ala Ala Glu Glu Thr Gly Gly Thr 35 40 45 Asn Thr Glu Ala Gln Pro LysThr Glu Ala Val Ala Ser Pro Thr Thr 50 55 60 Thr Ser Glu Lys Ala Pro GluThr Lys Pro Val Ala Asn Ala Val Ser 65 70 75 80 Val Ser Asn Lys Glu ValGlu Ala Pro Thr Ser Glu Thr Lys Glu Ala 85 90 95 Lys Glu Val Lys Glu ValLys Ala Pro Lys Glu Thr Lys Glu Val Lys 100 105 110 Pro Ala Ala Lys AlaThr Asn Asn Thr Tyr Pro Ile Leu Asn Gln Glu 115 120 125 Leu Ile Arg SerAsp 130 21 205 PRT Staphylococcus aureus 21 Asp His Gly Ile Val Phe AsnAla Ser Leu Pro Leu Tyr Lys Asp Ala 1 5 10 15 Ile His Gln Lys Gly SerMet Arg Ser Asn Asp Asn Gly Asp Asp Met 20 25 30 Ser Met Met Val Gly ThrVal Leu Ser Gly Phe Glu Tyr Arg Ala Gln 35 40 45 Lys Glu Lys Tyr Asp AsnLeu Tyr Lys Phe Phe Lys Glu Asn Glu Lys 50 55 60 Lys Tyr Gln Tyr Thr GlyPhe Thr Lys Glu Ala Ile Asn Lys Thr Gln 65 70 75 80 Asn Val Gly Tyr LysAsn Glu Tyr Phe Tyr Ile Thr Tyr Ser Ser Arg 85 90 95 Ser Leu Lys Glu TyrArg Lys Tyr Tyr Glu Pro Leu Ile Arg Lys Asn 100 105 110 Asp Lys Glu PheLys Glu Gly Met Glu Arg Ala Arg Lys Glu Val Asn 115 120 125 Tyr Ala AlaAsn Thr Asp Ala Val Ala Thr Leu Phe Ser Thr Lys Lys 130 135 140 Asn PheThr Lys Asp Asn Thr Val Asp Asp Val Ile Glu Leu Ser Asp 145 150 155 160Lys Leu Tyr Asn Leu Lys Asn Lys Pro Asp Lys Ser Thr Ile Thr Ile 165 170175 Gln Ile Gly Lys Pro Thr Ile Asn Thr Lys Lys Ala Phe Tyr Asp Asp 180185 190 Asn Arg Pro Ile Glu Tyr Gly Val His Ser Lys Asp Glu 195 200 20522 510 PRT Staphylococcus aureus 22 Asp His Tyr Val Ile Gln Tyr Phe SerGly Leu Ile Gly Gly Arg Gly 1 5 10 15 Arg Arg Ala Asn Leu Tyr Gly LeuPhe Asn Lys Ala Ile Glu Phe Glu 20 25 30 Asn Ser Ser Phe Arg Gly Leu TyrGln Phe Ile Arg Phe Ile Asp Glu 35 40 45 Leu Ile Glu Arg Gly Lys Asp PheGly Glu Glu Asn Val Val Gly Pro 50 55 60 Asn Asp Asn Val Val Arg Met MetThr Ile His Ser Ser Lys Gly Leu 65 70 75 80 Glu Phe Pro Phe Val Ile TyrSer Gly Leu Ser Lys Asp Phe Asn Lys 85 90 95 Arg Asp Leu Lys Gln Pro ValIle Leu Asn Gln Gln Phe Gly Leu Gly 100 105 110 Met Asp Tyr Phe Asp ValAsp Lys Glu Met Ala Phe Pro Ser Leu Ala 115 120 125 Ser Val Ala Tyr ArgAla Val Ala Glu Lys Glu Leu Val Ser Glu Glu 130 135 140 Met Arg Leu ValTyr Val Ala Leu Thr Arg Ala Lys Glu Gln Leu Tyr 145 150 155 160 Leu IleGly Arg Val Lys Asn Asp Lys Ser Leu Leu Glu Leu Glu Gln 165 170 175 LeuSer Ile Ser Gly Glu His Ile Ala Val Asn Glu Arg Leu Thr Ser 180 185 190Pro Asn Pro Phe His Leu Ile Tyr Ser Ile Leu Ser Lys His Gln Ser 195 200205 Ala Ser Ile Pro Asp Asp Leu Lys Phe Glu Lys Asp Ile Ala Gln Ile 210215 220 Glu Asp Ser Ser Arg Pro Asn Val Asn Ile Ser Ile Val Tyr Phe Glu225 230 235 240 Asp Val Ser Thr Glu Thr Ile Leu Asp Asn Asp Glu Tyr ArgSer Val 245 250 255 Asn Gln Leu Glu Thr Met Gln Asn Gly Asn Glu Asp ValLys Ala Gln 260 265 270 Ile Lys His Gln Leu Asp Tyr Arg Tyr Pro Tyr ValAsn Asp Thr Lys 275 280 285 Lys Pro Ser Lys Gln Ser Val Ser Glu Leu LysArg Gln Tyr Glu Thr 290 295 300 Glu Glu Ser Gly Thr Ser Tyr Glu Arg ValArg Gln Tyr Arg Ile Gly 305 310 315 320 Phe Ser Thr Tyr Glu Arg Pro LysPhe Leu Ser Glu Gln Gly Lys Arg 325 330 335 Lys Ala Asn Glu Ile Gly ThrLeu Met His Thr Val Met Gln His Leu 340 345 350 Pro Phe Lys Lys Glu ArgIle Ser Glu Val Glu Leu His Gln Tyr Ile 355 360 365 Asp Gly Leu Ile AspLys His Ile Ile Glu Ala Asp Ala Lys Lys Asp 370 375 380 Ile Arg Met AspGlu Ile Met Thr Phe Ile Asn Ser Glu Leu Tyr Ser 385 390 395 400 Ile IleAla Glu Ala Glu Gln Val Tyr Arg Glu Leu Pro Phe Val Val 405 410 415 AsnGln Ala Leu Val Asp Gln Leu Pro Gln Gly Asp Glu Asp Val Ser 420 425 430Ile Ile Gln Gly Met Ile Asp Leu Ile Phe Val Lys Asp Gly Val His 435 440445 Tyr Phe Val Asp Tyr Lys Thr Asp Ala Phe Asn Arg Arg Arg Gly Met 450455 460 Thr Asp Glu Glu Ile Gly Thr Gln Leu Lys Asn Lys Tyr Lys Ile Gln465 470 475 480 Met Lys Tyr Tyr Gln Asn Thr Leu Gln Thr Ile Leu Asn LysGlu Val 485 490 495 Lys Gly Tyr Leu Tyr Phe Phe Lys Phe Gly Thr Leu GlnLeu 500 505 510 23 124 PRT Staphylococcus aureus 23 Met Lys Phe Leu SerPhe Lys Tyr Asn Asp Lys Thr Ser Tyr Gly Val 1 5 10 15 Lys Val Lys ArgGlu Asp Ala Val Trp Asp Leu Thr Gln Val Phe Ala 20 25 30 Asp Phe Ala GluGly Asp Phe His Pro Lys Thr Leu Leu Ala Gly Leu 35 40 45 Gln Gln Asn HisThr Leu Asp Phe Gln Glu Gln Val Arg Lys Ala Val 50 55 60 Val Ala Ala GluAsp Ser Gly Lys Ala Glu Asp Tyr Lys Ile Ser Phe 65 70 75 80 Asn Asp IleGlu Phe Leu Pro Pro Val Thr Pro Pro Asn Asn Val Ile 85 90 95 Ala Phe GlyArg Asn Tyr Lys Asp His Ala Asn Glu Leu Asn His Glu 100 105 110 Val GluLys Leu Tyr Val Phe Thr Lys Ala Ala Ser 115 120 24 180 PRTStaphylococcus aureus 24 Ser Gly Thr Gly Phe Ile Val Gly Lys Asn Thr IleVal Thr Asn Lys 1 5 10 15 His Val Val Ala Gly Met Glu Ile Gly Ala HisIle Ile Ala His Pro 20 25 30 Asn Gly Glu Tyr Asn Asn Gly Gly Phe Tyr LysVal Lys Lys Ile Val 35 40 45 Arg Tyr Ser Gly Gln Glu Asp Ile Ala Ile LeuHis Val Glu Asp Lys 50 55 60 Ala Val His Pro Lys Asn Arg Asn Phe Lys AspTyr Thr Gly Ile Leu 65 70 75 80 Lys Ile Ala Ser Glu Ala Lys Glu Asn GluArg Ile Ser Ile Val Gly 85 90 95 Tyr Pro Glu Pro Tyr Ile Asn Lys Phe GlnMet Tyr Glu Ser Thr Gly 100 105 110 Lys Val Leu Ser Val Lys Gly Asn MetIle Ile Thr Asp Ala Phe Val 115 120 125 Glu Pro Gly Asn Ser Gly Ser AlaVal Phe Asn Ser Lys Tyr Glu Val 130 135 140 Val Gly Val His Phe Gly GlyAsn Gly Pro Gly Asn Lys Ser Thr Lys 145 150 155 160 Gly Tyr Gly Val TyrPhe Ser Pro Glu Ile Lys Lys Phe Ile Ala Asp 165 170 175 Asn Thr Asp Lys180 25 239 PRT Staphylococcus aureus 25 Met Asn Lys Asn Ile Ile Ile LysSer Ile Ala Ala Leu Thr Ile Leu 1 5 10 15 Thr Ser Ile Thr Gly Val GlyThr Thr Met Val Glu Gly Ile Gln Gln 20 25 30 Thr Ala Lys Ala Glu Asn ThrVal Lys Gln Ile Thr Asn Thr Asn Val 35 40 45 Ala Pro Tyr Ser Gly Val ThrTrp Met Gly Ala Gly Thr Gly Phe Val 50 55 60 Val Gly Asn His Thr Ile IleThr Asn Lys His Val Thr Tyr His Met 65 70 75 80 Lys Val Gly Asp Glu IleLys Ala His Pro Asn Gly Phe Tyr Asn Asn 85 90 95 Gly Gly Gly Leu Tyr LysVal Thr Lys Ile Val Asp Tyr Pro Gly Lys 100 105 110 Glu Asp Ile Ala ValVal Gln Val Glu Glu Lys Ser Thr Gln Pro Lys 115 120 125 Gly Arg Lys PheLys Asp Phe Thr Ser Lys Phe Asn Ile Ala Ser Glu 130 135 140 Ala Lys GluAsn Glu Pro Ile Ser Val Ile Gly Tyr Pro Asn Pro Asn 145 150 155 160 GlyAsn Lys Leu Gln Met Tyr Glu Ser Thr Gly Lys Val Leu Ser Val 165 170 175Asn Gly Asn Ile Val Ser Ser Asp Ala Ile Ile Gln Pro Gly Ser Ser 180 185190 Gly Ser Pro Ile Leu Asn Ser Lys His Glu Ala Ile Gly Val Ile Tyr 195200 205 Ala Gly Asn Lys Pro Ser Gly Glu Ser Thr Arg Gly Phe Ala Val Tyr210 215 220 Phe Ser Pro Glu Ile Lys Lys Phe Ile Ala Asp Asn Leu Asp Lys225 230 235 26 470 PRT Staphylococcus aureus 26 Met Gly Cys Thr Val LysMet Asn Lys Ile Asn Asp Arg Asp Leu Thr 1 5 10 15 Glu Leu Ser Ser TyrTrp Val Tyr Gln Asn Ile Asp Ile Lys Lys Glu 20 25 30 Phe Lys Val Asn GlyLys Arg Phe Lys Gln Val Asp Ser Tyr Asn Asp 35 40 45 Asp Lys Asn Ser AsnLeu Asn Gly Ala Ala Asp Ile Lys Ile Tyr Glu 50 55 60 Leu Leu Asp Asp LysSer Lys Pro Thr Gly Gln Gln Thr Ile Ile Tyr 65 70 75 80 Gln Gly Thr SerAsn Glu Ala Ile Asn Pro Asn Asn Pro Leu Lys Ser 85 90 95 Ser Gly Phe GlyAsp Asp Trp Leu Gln Asn Ala Lys Leu Met Asn Asn 100 105 110 Asp Asn GluSer Thr Asp Tyr Leu Lys Gln Thr Asp Gln Leu Ser Asn 115 120 125 Gln TyrLys Ile Lys Leu Glu Asp Ala Asp Arg Leu Ser Asn Ser Asp 130 135 140 PheLeu Lys Lys Tyr Arg Met Glu Ser Ser Asn Phe Lys Asn Lys Thr 145 150 155160 Ile Val Ala Asp Gly Gly Asn Ser Glu Gly Gly Ala Gly Ala Lys Tyr 165170 175 Gln Gly Ala Lys His Pro Asn Glu Lys Val Val Ala Thr Asp Ser Ala180 185 190 Met Ile Pro Tyr Ala Ala Trp Gln Lys Phe Ala Arg Pro Arg PheAsp 195 200 205 Asn Met Ile Ser Phe Asn Ser Thr Asn Asp Leu Leu Thr TrpLeu Gln 210 215 220 Asp Pro Phe Ile Lys Asp Met Pro Gly Lys Arg Val AsnIle Asn Asp 225 230 235 240 Gly Val Pro Arg Leu Asp Thr Leu Ile Asp SerHis Val Gly Tyr Lys 245 250 255 Arg Lys Leu Asn Arg Lys Asp Asn Thr TyrAsp Thr Val Pro Leu Ile 260 265 270 Lys Ile Lys Ser Val Lys Asp Thr GluIle Lys Asn Gly Lys Lys Val 275 280 285 Lys Lys Thr Ile Asn Ile Thr LeuAsp Met Asp Gly Arg Ile Pro Ile 290 295 300 Asn Val Trp Thr Gly Asp SerIle Ala Arg Ser Gly Arg Gly Thr Leu 305 310 315 320 Ile Lys Leu Asn LeuGlu Asn Leu Asp Ala Leu Ser Lys Leu Ile Thr 325 330 335 Gly Glu Thr SerGly Met Leu Ala Glu Cys Val Ile Phe Leu Asn Glu 340 345 350 Ser Phe AsnIle Ser Glu Asn Glu Asn Lys Asn Phe Ala Asp Arg Lys 355 360 365 Lys GlnLeu Ser Glu Gly Phe Lys Asp Lys Ile Asn Leu Phe Gln Leu 370 375 380 GluGlu Met Glu Arg Thr Leu Ile Ser Lys Ile Asn Ser Leu Glu Glu 385 390 395400 Val Ala Asp Glu Thr Ile Glu Ser Ile Ser Ala Val Lys His Leu Leu 405410 415 Pro Asp Phe Ala Leu Asp Ala Leu Lys Glu Arg Ile Asn Glu Leu Phe420 425 430 Lys Gly Ile Lys Ser Phe Ile Glu Lys Val Tyr Asp Ser Ile AspAsn 435 440 445 Glu Ile Leu Glu Ile Phe Lys Asn Ile Asp His Asp Phe ArgAsp Gly 450 455 460 Val Ser Glu Glu Met Met 465 470 27 306 PRTStaphylococcus aureus 27 Met Lys Lys Lys Asp Gly Thr Gln Gln Phe Tyr HisTyr Ala Ser Ser 1 5 10 15 Val Lys Pro Ala Arg Val Ile Phe Thr Asp SerLys Pro Glu Ile Glu 20 25 30 Leu Gly Leu Gln Ser Gly Gln Phe Trp Arg LysPhe Glu Val Tyr Glu 35 40 45 Gly Asp Lys Lys Leu Pro Ile Lys Leu Val SerTyr Asp Thr Val Lys 50 55 60 Asp Tyr Ala Tyr Ile Arg Phe Ser Val Ser AsnGly Thr Lys Ala Val 65 70 75 80 Lys Ile Val Ser Ser Thr His Phe Asn AsnLys Glu Glu Lys Tyr Asp 85 90 95 Tyr Thr Leu Met Glu Phe Ala Gln Pro IleTyr Asn Ser Ala Asp Lys 100 105 110 Phe Lys Thr Glu Glu Asp Tyr Lys AlaGlu Lys Leu Leu Ala Pro Tyr 115 120 125 Lys Lys Ala Lys Thr Leu Glu ArgGln Val Tyr Glu Leu Asn Lys Ile 130 135 140 Gln Asp Lys Leu Pro Glu LysLeu Lys Ala Glu Tyr Lys Lys Lys Leu 145 150 155 160 Glu Asp Thr Lys LysAla Leu Asp Glu Gln Val Lys Ser Ala Ile Thr 165 170 175 Glu Phe Gln AsnVal Gln Pro Thr Asn Glu Lys Met Thr Asp Leu Gln 180 185 190 Asp Thr LysTyr Val Val Tyr Glu Ser Val Glu Asn Asn Glu Ser Met 195 200 205 Met AspThr Phe Val Lys His Pro Ile Lys Thr Gly Met Leu Asn Gly 210 215 220 LysLys Tyr Met Val Met Glu Thr Thr Asn Asp Asp Tyr Trp Lys Asp 225 230 235240 Phe Met Val Glu Gly Gln Arg Val Arg Thr Ile Ser Lys Asp Ala Lys 245250 255 Asn Asn Thr Arg Thr Ile Ile Phe Pro Tyr Val Glu Gly Lys Thr Leu260 265 270 Tyr Asp Ala Ile Val Lys Val His Val Lys Thr Ile Asp Tyr AspGly 275 280 285 Gln Tyr His Val Arg Ile Val Asp Lys Glu Ala Phe Thr LysAla His 290 295 300 Thr Asp 305 28 2659 PRT Staphylococcus aureus 28 AspGln Thr Thr Ile Ile Asn Ser Leu Thr Phe Thr Glu Thr Val Pro 1 5 10 15Asn Arg Ser Tyr Ala Arg Ala Ser Ala Asn Glu Ile Thr Ser Lys Thr 20 25 30Val Ser Asn Val Ser Arg Thr Gly Asn Asn Ala Asn Val Thr Val Thr 35 40 45Val Thr Tyr Gln Asp Gly Thr Thr Ser Thr Val Thr Val Pro Val Lys 50 55 60His Val Ile Pro Glu Ile Val Ala His Ser His Tyr Thr Val Gln Gly 65 70 7580 Gln Asp Phe Pro Ala Gly Asn Gly Ser Ser Ala Ser Asp Tyr Phe Lys 85 9095 Leu Ser Asn Gly Ser Asp Ile Ala Asp Ala Thr Ile Thr Trp Val Ser 100105 110 Gly Gln Ala Pro Asn Lys Asp Asn Thr Arg Ile Gly Glu Asp Ile Thr115 120 125 Val Thr Ala His Ile Leu Ile Asp Gly Glu Thr Thr Pro Ile ThrLys 130 135 140 Thr Ala Thr Tyr Lys Val Val Arg Thr Val Pro Lys His ValPhe Glu 145 150 155 160 Thr Ala Arg Gly Val Leu Tyr Pro Gly Val Ser AspMet Tyr Asp Ala 165 170 175 Lys Gln Tyr Val Lys Pro Val Asn Asn Ser TrpSer Thr Asn Ala Gln 180 185 190 His Met Asn Phe Gln Phe Val Gly Thr TyrGly Pro Asn Lys Asp Val 195 200 205 Val Gly Ile Ser Thr Arg Leu Ile ArgVal Thr Tyr Asp Asn Arg Gln 210 215 220 Thr Glu Asp Leu Thr Ile Leu SerLys Val Lys Pro Asp Pro Pro Arg 225 230 235 240 Ile Asp Ala Asn Ser ValThr Tyr Lys Ala Gly Leu Thr Asn Gln Glu 245 250 255 Ile Lys Val Asn AsnVal Leu Asn Asn Ser Ser Val Lys Leu Phe Lys 260 265 270 Ala Asp Asn ThrPro Leu Asn Val Thr Asn Ile Thr His Gly Ser Gly 275 280 285 Phe Ser SerVal Val Thr Val Ser Asp Ala Leu Pro Asn Gly Gly Ile 290 295 300 Lys AlaLys Ser Ser Ile Ser Met Asn Asn Val Thr Tyr Thr Thr Gln 305 310 315 320Asp Glu His Gly Gln Val Val Thr Val Thr Arg Asn Glu Ser Val Asp 325 330335 Ser Asn Asp Ser Ala Thr Val Thr Val Thr Pro Gln Leu Gln Ala Thr 340345 350 Thr Glu Gly Ala Val Phe Ile Lys Gly Gly Asp Gly Phe Asp Phe Gly355 360 365 His Val Glu Arg Phe Ile Gln Asn Pro Pro His Gly Ala Thr ValAla 370 375 380 Trp His Asp Ser Pro Asp Thr Trp Lys Asn Thr Val Gly AsnThr His 385 390 395 400 Lys Thr Ala Val Val Thr Leu Pro Asn Gly Gln GlyThr Arg Asn Val 405 410 415 Glu Val Pro Val Lys Val Tyr Pro Val Ala AsnAla Lys Ala Pro Ser 420 425 430 Arg Asp Val Lys Gly Gln Asn Leu Thr AsnGly Thr Asp Ala Met Asn 435 440 445 Tyr Ile Thr Phe Asp Pro Asn Thr AsnThr Asn Gly Ile Thr Ala Ala 450 455 460 Trp Ala Asn Arg Gln Gln Pro AsnAsn Gln Gln Ala Gly Val Gln His 465 470 475 480 Leu Asn Val Asp Val ThrTyr Pro Gly Ile Ser Ala Ala Lys Arg Val 485 490 495 Pro Val Thr Val AsnVal Tyr Gln Phe Glu Phe Pro Gln Thr Thr Tyr 500 505 510 Thr Thr Thr ValGly Gly Thr Leu Ala Ser Gly Thr Gln Ala Ser Gly 515 520 525 Tyr Ala HisMet Gln Asn Ala Thr Gly Leu Pro Thr Asp Gly Phe Thr 530 535 540 Tyr LysTrp Asn Arg Asp Thr Thr Gly Thr Asn Asp Ala Asn Trp Ser 545 550 555 560Ala Met Asn Lys Pro Asn Val Ala Lys Val Val Asn Ala Lys Tyr Asp 565 570575 Val Ile Tyr Asn Gly His Thr Phe Ala Thr Ser Leu Pro Ala Lys Phe 580585 590 Val Val Lys Asp Val Gln Pro Ala Lys Pro Thr Val Thr Glu Thr Ala595 600 605 Ala Gly Ala Ile Thr Ile Ala Pro Gly Ala Asn Gln Thr Val AsnThr 610 615 620 His Ala Gly Asn Val Thr Thr Tyr Ala Asp Lys Leu Val IleLys Arg 625 630 635 640 Asn Gly Asn Val Val Thr Thr Phe Thr Arg Arg AsnAsn Thr Ser Pro 645 650 655 Trp Val Lys Glu Ala Ser Ala Ala Thr Val AlaGly Ile Ala Gly Thr 660 665 670 Asn Asn Gly Ile Thr Val Ala Ala Gly ThrPhe Asn Pro Ala Asp Thr 675 680 685 Ile Gln Val Val Ala Thr Gln Gly SerGly Glu Thr Val Ser Asp Glu 690 695 700 Gln Arg Ser Asp Asp Phe Thr ValVal Ala Pro Gln Pro Asn Gln Ala 705 710 715 720 Thr Thr Lys Ile Trp GlnAsn Gly His Ile Asp Ile Thr Pro Asn Asn 725 730 735 Pro Ser Gly His LeuIle Asn Pro Thr Gln Ala Met Asp Ile Ala Tyr 740 745 750 Thr Glu Lys ValGly Asn Gly Ala Glu His Ser Lys Thr Ile Asn Val 755 760 765 Val Arg GlyGln Asn Asn Gln Trp Thr Ile Ala Asn Lys Pro Asp Tyr 770 775 780 Val ThrLeu Asp Ala Gln Thr Gly Lys Val Thr Phe Asn Ala Asn Thr 785 790 795 800Ile Lys Pro Asn Ser Ser Ile Thr Ile Thr Pro Lys Ala Gly Thr Gly 805 810815 His Ser Val Ser Ser Asn Pro Ser Thr Leu Thr Ala Pro Ala Ala His 820825 830 Thr Val Asn Thr Thr Glu Ile Val Lys Asp Tyr Gly Ser Asn Val Thr835 840 845 Ala Ala Glu Ile Asn Asn Ala Val Gln Val Ala Asn Lys Arg ThrAla 850 855 860 Thr Ile Lys Asn Gly Thr Ala Met Pro Thr Asn Leu Ala GlyGly Ser 865 870 875 880 Thr Thr Thr Ile Pro Val Thr Val Thr Tyr Asn AspGly Ser Thr Glu 885 890 895 Glu Val Gln Glu Ser Ile Phe Thr Lys Ala AspLys Arg Glu Leu Ile 900 905 910 Thr Ala Lys Asn His Leu Asp Asp Pro ValSer Thr Glu Gly Lys Lys 915 920 925 Pro Gly Thr Ile Thr Gln Tyr Asn AsnAla Met His Asn Ala Gln Gln 930 935 940 Gln Ile Asn Thr Ala Lys Thr GluAla Gln Gln Val Ile Asn Asn Glu 945 950 955 960 Arg Ala Thr Pro Gln GlnVal Ser Asp Ala Leu Thr Lys Val Arg Ala 965 970 975 Ala Gln Thr Lys IleAsp Gln Ala Lys Ala Leu Leu Gln Asn Lys Glu 980 985 990 Asp Asn Ser GlnLeu Val Thr Ser Lys Asn Asn Leu Gln Ser Ser Val 995 1000 1005 Asn GlnVal Pro Ser Thr Ala Gly Met Thr Gln Gln Ser Ile Asp Asn 1010 1015 1020Tyr Asn Ala Lys Lys Arg Glu Ala Glu Thr Glu Ile Thr Ala Ala Gln 10251030 1035 1040 Arg Val Ile Asp Asn Gly Asp Ala Thr Ala Gln Gln Ile SerAsp Glu 1045 1050 1055 Lys His Arg Val Asp Asn Ala Leu Thr Ala Leu AsnGln Ala Lys His 1060 1065 1070 Asp Leu Thr Ala Asp Thr His Ala Leu GluGln Ala Val Gln Gln Leu 1075 1080 1085 Asn Arg Thr Gly Thr Thr Thr GlyLys Lys Pro Ala Ser Ile Thr Ala 1090 1095 1100 Tyr Asn Asn Ser Ile ArgAla Leu Gln Ser Asp Leu Thr Ser Ala Lys 1105 1110 1115 1120 Asn Ser AlaAsn Ala Ile Ile Gln Lys Pro Ile Arg Thr Val Gln Glu 1125 1130 1135 ValGln Ser Ala Leu Thr Asn Val Asn Arg Val Asn Glu Arg Leu Thr 1140 11451150 Gln Ala Ile Asn Gln Leu Val Pro Leu Ala Asp Asn Ser Ala Leu Lys1155 1160 1165 Thr Ala Lys Thr Lys Leu Asp Glu Glu Ile Asn Lys Ser ValThr Thr 1170 1175 1180 Asp Gly Met Thr Gln Ser Ser Ile Gln Ala Tyr GluAsn Ala Lys Arg 1185 1190 1195 1200 Ala Gly Gln Thr Glu Ser Thr Asn AlaGln Asn Val Ile Asn Asn Gly 1205 1210 1215 Asp Ala Thr Asp Gln Gln IleAla Ala Glu Lys Thr Lys Val Glu Glu 1220 1225 1230 Lys Tyr Asn Ser LeuLys Gln Ala Ile Ala Gly Leu Thr Pro Asp Leu 1235 1240 1245 Ala Pro LeuGln Thr Ala Lys Thr Gln Leu Gln Asn Asp Ile Asp Gln 1250 1255 1260 ProThr Ser Thr Thr Gly Met Thr Ser Ala Ser Ile Ala Ala Phe Asn 1265 12701275 1280 Glu Lys Leu Ser Ala Ala Arg Thr Lys Ile Gln Glu Ile Asp ArgVal 1285 1290 1295 Leu Ala Ser His Pro Asp Val Ala Thr Ile Arg Gln AsnVal Thr Ala 1300 1305 1310 Ala Asn Ala Ala Lys Ser Ala Leu Asp Gln AlaArg Asn Gly Leu Thr 1315 1320 1325 Val Asp Lys Ala Pro Leu Glu Asn AlaLys Asn Gln Leu Gln Tyr Ser 1330 1335 1340 Ile Asp Thr Gln Thr Ser ThrThr Gly Met Thr Gln Asp Ser Ile Asn 1345 1350 1355 1360 Ala Tyr Asn AlaLys Leu Thr Ala Ala Arg Asn Lys Ile Gln Gln Ile 1365 1370 1375 Asn GlnVal Leu Ala Gly Ser Pro Thr Val Glu Gln Ile Asn Thr Asn 1380 1385 1390Thr Ser Thr Ala Asn Gln Ala Lys Ser Asp Leu Asp His Ala Arg Gln 13951400 1405 Ala Leu Thr Pro Asp Lys Ala Pro Leu Gln Thr Ala Lys Thr GlnLeu 1410 1415 1420 Glu Gln Ser Ile Asn Gln Pro Thr Asp Thr Thr Gly MetThr Thr Ala 1425 1430 1435 1440 Ser Leu Asn Ala Tyr Asn Gln Lys Leu GlnAla Ala Arg Gln Lys Leu 1445 1450 1455 Thr Glu Ile Asn Gln Val Leu AsnGly Asn Pro Thr Val Gln Asn Ile 1460 1465 1470 Asn Asp Lys Val Thr GluAla Asn Gln Ala Lys Asp Gln Leu Asn Thr 1475 1480 1485 Ala Arg Gln GlyLeu Thr Leu Asp Arg Gln Pro Ala Leu Thr Thr Leu 1490 1495 1500 His GlyAla Ser Asn Leu Asn Gln Ala Gln Gln Asn Asn Phe Thr Gln 1505 1510 15151520 Gln Ile Asn Ala Ala Gln Asn His Ala Ala Leu Glu Thr Ile Lys Ser1525 1530 1535 Asn Ile Thr Ala Leu Asn Thr Ala Met Thr Lys Leu Lys AspSer Val 1540 1545 1550 Ala Asp Asn Asn Thr Ile Lys Ser Asp Gln Asn TyrThr Asp Ala Thr 1555 1560 1565 Pro Ala Asn Lys Gln Ala Tyr Asp Asn AlaVal Asn Ala Ala Lys Gly 1570 1575 1580 Val Ile Gly Glu Thr Thr Asn ProThr Met Asp Val Asn Thr Val Asn 1585 1590 1595 1600 Gln Lys Ala Ala SerVal Lys Ser Thr Lys Asp Ala Leu Asp Gly Gln 1605 1610 1615 Gln Asn LeuGln Arg Ala Lys Thr Glu Ala Thr Asn Ala Ile Thr His 1620 1625 1630 AlaSer Asp Leu Asn Gln Ala Gln Lys Asn Ala Leu Thr Gln Gln Val 1635 16401645 Asn Ser Ala Gln Asn Val Gln Ala Val Asn Asp Ile Lys Gln Thr Thr1650 1655 1660 Gln Ser Leu Asn Thr Ala Met Thr Gly Leu Lys Arg Gly ValAla Asn 1665 1670 1675 1680 His Asn Gln Val Val Gln Ser Asp Asn Tyr ValAsn Ala Asp Thr Asn 1685 1690 1695 Lys Lys Asn Asp Tyr Asn Asn Ala TyrAsn His Ala Asn Asp Ile Ile 1700 1705 1710 Asn Gly Asn Ala Gln His ProVal Ile Thr Pro Ser Asp Val Asn Asn 1715 1720 1725 Ala Leu Ser Asn ValThr Ser Lys Glu His Ala Leu Asn Gly Glu Ala 1730 1735 1740 Lys Leu AsnAla Ala Lys Gln Glu Ala Asn Thr Ala Leu Gly His Leu 1745 1750 1755 1760Asn Asn Leu Asn Asn Ala Gln Arg Gln Asn Leu Gln Ser Gln Ile Asn 17651770 1775 Gly Ala His Gln Ile Asp Ala Val Asn Thr Ile Lys Gln Asn AlaThr 1780 1785 1790 Asn Leu Asn Ser Ala Met Gly Asn Leu Arg Gln Ala ValAla Asp Lys 1795 1800 1805 Asp Gln Val Lys Arg Thr Glu Asp Tyr Ala AspAla Asp Thr Ala Lys 1810 1815 1820 Gln Asn Ala Tyr Asn Ser Ala Val SerSer Ala Glu Thr Ile Ile Asn 1825 1830 1835 1840 Gln Thr Thr Asn Pro ThrMet Ser Val Asp Asp Val Asn Arg Ala Thr 1845 1850 1855 Ser Ala Val ThrSer Asn Lys Asn Ala Leu Asn Gly Tyr Glu Lys Leu 1860 1865 1870 Ala GlnSer Lys Thr Asp Ala Ala Arg Ala Ile Asp Ala Leu Pro His 1875 1880 1885Leu Asn Asn Ala Gln Lys Ala Asp Val Lys Ser Lys Ile Asn Ala Ala 18901895 1900 Ser Asn Ile Ala Gly Val Asn Thr Val Lys Gln Gln Gly Thr AspLeu 1905 1910 1915 1920 Asn Thr Ala Met Gly Asn Leu Gln Gly Ala Ile AsnAsp Glu Gln Thr 1925 1930 1935 Thr Leu Asn Ser Gln Asn Tyr Gln Asp AlaThr Pro Ser Lys Lys Thr 1940 1945 1950 Ala Tyr Thr Asn Ala Val Gln AlaAla Lys Asp Ile Leu Asn Lys Ser 1955 1960 1965 Asn Gly Gln Asn Lys ThrLys Asp Gln Val Thr Glu Ala Met Asn Gln 1970 1975 1980 Val Asn Ser AlaLys Asn Asn Leu Asp Gly Thr Arg Leu Leu Asp Gln 1985 1990 1995 2000 AlaLys Gln Thr Ala Lys Gln Gln Leu Asn Asn Met Thr His Leu Thr 2005 20102015 Thr Ala Gln Lys Thr Asn Leu Thr Asn Gln Ile Asn Ser Gly Thr Thr2020 2025 2030 Val Ala Gly Val Gln Thr Val Gln Ser Asn Ala Asn Thr LeuAsp Gln 2035 2040 2045 Ala Met Asn Thr Leu Arg Gln Ser Ile Ala Asn LysAsp Ala Thr Lys 2050 2055 2060 Ala Ser Glu Asp Tyr Val Asp Ala Asn AsnAsp Lys Gln Thr Ala Tyr 2065 2070 2075 2080 Asn Asn Ala Val Ala Ala AlaGlu Thr Ile Ile Asn Ala Asn Ser Asn 2085 2090 2095 Pro Glu Met Asn ProSer Thr Ile Thr Gln Lys Ala Glu Gln Val Asn 2100 2105 2110 Ser Ser LysThr Ala Leu Asn Gly Asp Glu Asn Leu Ala Ala Ala Lys 2115 2120 2125 GlnAsn Ala Lys Thr Tyr Leu Asn Thr Leu Thr Ser Ile Thr Asp Ala 2130 21352140 Gln Lys Asn Asn Leu Ile Ser Gln Ile Thr Ser Ala Thr Arg Val Ser2145 2150 2155 2160 Gly Val Asp Thr Val Lys Gln Asn Ala Gln His Leu AspGln Ala Met 2165 2170 2175 Ala Ser Leu Gln Asn Gly Ile Asn Asn Glu SerGln Val Lys Ser Ser 2180 2185 2190 Glu Lys Tyr Arg Asp Ala Asp Thr AsnLys Gln Gln Glu Tyr Asp Asn 2195 2200 2205 Ala Ile Thr Ala Ala Lys AlaIle Leu Asn Lys Ser Thr Gly Pro Asn 2210 2215 2220 Thr Ala Gln Asn AlaVal Glu Ala Ala Leu Gln Arg Val Asn Asn Ala 2225 2230 2235 2240 Lys AspAla Leu Asn Gly Asp Ala Lys Leu Ile Ala Ala Gln Asn Ala 2245 2250 2255Ala Lys Gln His Leu Gly Thr Leu Thr His Ile Thr Thr Ala Gln Arg 22602265 2270 Asn Asp Leu Thr Asn Gln Ile Ser Gln Ala Thr Asn Leu Ala GlyVal 2275 2280 2285 Glu Ser Val Lys Gln Asn Ala Asn Ser Leu Asp Gly AlaMet Gly Asn 2290 2295 2300 Leu Gln Thr Ala Ile Asn Asp Lys Ser Gly ThrLeu Ala Ser Gln Asn 2305 2310 2315 2320 Phe Leu Asp Ala Asp Glu Gln LysArg Asn Ala Tyr Asn Gln Ala Val 2325 2330 2335 Ser Ala Ala Glu Thr IleLeu Asn Lys Gln Thr Gly Pro Asn Thr Ala 2340 2345 2350 Lys Thr Ala ValGlu Gln Ala Leu Asn Asn Val Asn Asn Ala Lys His 2355 2360 2365 Ala LeuAsn Gly Thr Gln Asn Leu Asn Asn Ala Lys Gln Ala Ala Ile 2370 2375 2380Thr Ala Ile Asn Gly Ala Ser Asp Leu Asn Gln Lys Gln Lys Asp Ala 23852390 2395 2400 Leu Lys Ala Gln Ala Asn Gly Ala Gln Arg Val Ser Asn AlaGln Asp 2405 2410 2415 Val Gln His Asn Ala Thr Glu Leu Asn Thr Ala MetGly Thr Leu Lys 2420 2425 2430 His Ala Ile Ala Asp Lys Thr Asn Thr LeuAla Ser Ser Lys Tyr Val 2435 2440 2445 Asn Ala Asp Ser Thr Lys Gln AsnAla Tyr Thr Thr Lys Val Thr Asn 2450 2455 2460 Ala Glu His Ile Ile SerGly Thr Pro Thr Val Val Thr Thr Pro Ser 2465 2470 2475 2480 Glu Val ThrAla Ala Ala Asn Gln Val Asn Ser Ala Lys Gln Glu Leu 2485 2490 2495 AsnGly Asp Glu Arg Leu Arg Glu Ala Lys Gln Asn Ala Asn Thr Ala 2500 25052510 Ile Asp Ala Leu Thr Gln Leu Asn Thr Pro Gln Lys Ala Lys Leu Lys2515 2520 2525 Glu Gln Val Gly Gln Ala Asn Arg Leu Glu Asp Val Gln ThrVal Gln 2530 2535 2540 Thr Asn Gly Gln Ala Leu Asn Asn Ala Met Lys GlyLeu Arg Asp Ser 2545 2550 2555 2560 Ile Ala Asn Glu Thr Thr Val Lys ThrSer Gln Asn Tyr Thr Asp Ala 2565 2570 2575 Ser Pro Asn Asn Gln Ser ThrTyr Asn Ser Ala Val Ser Asn Ala Lys 2580 2585 2590 Gly Ile Ile Asn GlnThr Asn Asn Pro Thr Met Asp Thr Ser Ala Ile 2595 2600 2605 Thr Gln AlaThr Thr Gln Val Asn Asn Ala Lys Asn Gly Leu Asn Gly 2610 2615 2620 AlaGlu Asn Leu Arg Asn Ala Gln Asn Thr Ala Lys Gln Asn Leu Asn 2625 26302635 2640 Thr Leu Ser His Leu Thr Asn Asn Gln Lys Ser Ala Ile Ser SerGln 2645 2650 2655 Ile Asp Arg 29 496 PRT Staphylococcus aureus 29 MetAsn Met Lys Lys Lys Glu Lys His Ala Ile Arg Lys Lys Ser Ile 1 5 10 15Gly Val Ala Ser Val Leu Val Gly Thr Leu Ile Gly Phe Gly Leu Leu 20 25 30Ser Ser Lys Glu Ala Asp Ala Ser Glu Asn Ser Val Thr Gln Ser Asp 35 40 45Ser Ala Ser Asn Glu Ser Lys Ser Asn Asp Ser Ser Ser Val Ser Ala 50 55 60Ala Pro Lys Thr Asp Asp Thr Asn Val Ser Asp Thr Lys Thr Ser Ser 65 70 7580 Asn Thr Asn Asn Gly Glu Thr Ser Val Ala Gln Asn Pro Ala Gln Gln 85 9095 Glu Thr Thr Gln Ser Ser Ser Thr Asn Ala Thr Thr Glu Glu Thr Pro 100105 110 Val Thr Gly Glu Ala Thr Thr Thr Thr Thr Asn Gln Ala Asn Thr Pro115 120 125 Ala Thr Thr Gln Ser Ser Asn Thr Asn Ala Glu Glu Leu Val AsnGln 130 135 140 Thr Ser Asn Glu Thr Thr Phe Asn Asp Thr Asn Thr Val SerSer Val 145 150 155 160 Asn Ser Pro Gln Asn Ser Thr Asn Ala Glu Asn ValSer Thr Thr Gln 165 170 175 Asp Thr Ser Thr Glu Ala Thr Pro Ser Asn AsnGlu Ser Ala Pro Gln 180 185 190 Ser Thr Asp Ala Ser Asn Lys Asp Val ValAsn Gln Ala Val Asn Thr 195 200 205 Ser Ala Pro Arg Met Arg Ala Phe SerLeu Ala Ala Val Ala Ala Asp 210 215 220 Ala Pro Ala Ala Gly Thr Asp IleThr Asn Gln Leu Thr Asn Val Thr 225 230 235 240 Val Gly Ile Asp Ser GlyThr Thr Val Tyr Pro His Gln Ala Gly Tyr 245 250 255 Val Lys Leu Asn TyrGly Phe Ser Val Pro Asn Ser Ala Val Lys Gly 260 265 270 Asp Thr Phe LysIle Thr Val Pro Lys Glu Leu Asn Leu Asn Gly Val 275 280 285 Thr Ser ThrAla Lys Val Pro Pro Ile Met Ala Gly Asp Gln Val Leu 290 295 300 Ala AsnGly Val Ile Asp Ser Asp Gly Asn Val Ile Tyr Thr Phe Thr 305 310 315 320Asp Tyr Val Asn Thr Lys Asp Asp Val Lys Ala Thr Leu Thr Met Pro 325 330335 Ala Tyr Ile Asp Pro Glu Asn Val Lys Lys Thr Gly Asn Val Thr Leu 340345 350 Ala Thr Gly Ile Gly Ser Thr Thr Ala Asn Lys Thr Val Leu Val Asp355 360 365 Tyr Glu Lys Tyr Gly Lys Phe Tyr Asn Leu Ser Ile Lys Gly ThrIle 370 375 380 Asp Gln Ile Asp Lys Thr Asn Asn Thr Tyr Arg Gln Thr IleTyr Val 385 390 395 400 Asn Pro Ser Gly Asp Asn Val Ile Ala Pro Val LeuThr Gly Asn Leu 405 410 415 Lys Pro Asn Thr Asp Ser Asn Ala Leu Ile AspGln Gln Asn Thr Ser 420 425 430 Ile Lys Val Tyr Lys Val Asp Asn Ala AlaAsp Leu Ser Glu Ser Tyr 435 440 445 Phe Val Asn Pro Glu Asn Phe Glu AspVal Thr Asn Ser Val Asn Ile 450 455 460 Thr Phe Pro Asn Pro Asn Gln TyrLys Val Glu Phe Asn Thr Pro Asp 465 470 475 480 Asp Gln Ile Thr Thr ProTyr Ile Val Val Val Asn Gly His Ile Asp 485 490 495 30 541 PRTStaphylococcus aureus 30 Asp Gln Tyr Leu Leu Glu Arg Lys Lys Ser Gln TyrGlu Asp Tyr Lys 1 5 10 15 Gln Trp Tyr Ala Asn Tyr Lys Lys Glu Asn ProArg Thr Asp Leu Lys 20 25 30 Met Ala Asn Phe His Lys Tyr Asn Leu Glu GluLeu Ser Met Lys Glu 35 40 45 Tyr Asn Glu Leu Gln Asp Ala Leu Lys Arg AlaLeu Asp Asp Phe His 50 55 60 Arg Glu Val Lys Asp Ile Lys Asp Lys Asn SerAsp Leu Lys Thr Phe 65 70 75 80 Asn Ala Ala Glu Glu Asp Lys Ala Thr LysGlu Val Tyr Asp Leu Val 85 90 95 Ser Glu Ile Asp Thr Leu Val Val Ser TyrTyr Gly Asp Lys Asp Tyr 100 105 110 Gly Glu His Ala Lys Glu Leu Arg AlaLys Leu Asp Leu Ile Leu Gly 115 120 125 Asp Thr Asp Asn Pro His Lys IleThr Asn Glu Arg Ile Lys Lys Glu 130 135 140 Met Ile Asp Asp Leu Asn SerIle Ile Asp Asp Phe Phe Met Glu Thr 145 150 155 160 Lys Gln Asn Arg ProLys Ser Ile Thr Lys Tyr Asn Pro Thr Thr His 165 170 175 Asn Tyr Lys ThrAsn Ser Asp Asn Lys Pro Asn Phe Asp Lys Leu Val 180 185 190 Glu Glu ThrLys Lys Ala Val Lys Glu Ala Asp Asp Ser Trp Lys Lys 195 200 205 Lys ThrVal Lys Lys Tyr Gly Glu Thr Glu Thr Lys Ser Pro Val Val 210 215 220 LysGlu Glu Lys Lys Val Glu Glu Pro Gln Ala Pro Lys Val Asp Asn 225 230 235240 Gln Gln Glu Val Lys Thr Thr Ala Gly Lys Ala Glu Glu Thr Thr Gln 245250 255 Pro Val Ala Gln Pro Leu Val Lys Ile Pro Gln Gly Thr Ile Thr Gly260 265 270 Glu Ile Val Lys Gly Pro Glu Tyr Pro Thr Met Glu Asn Lys ThrVal 275 280 285 Gln Gly Glu Ile Val Gln Gly Pro Asp Phe Leu Thr Met GluGln Ser 290 295 300 Gly Pro Ser Leu Ser Asn Asn Tyr Thr Asn Pro Pro LeuThr Asn Pro 305 310 315 320 Ile Leu Glu Gly Leu Glu Gly Ser Ser Ser LysLeu Glu Ile Lys Pro 325 330 335 Gln Gly Thr Glu Ser Thr Leu Lys Gly ThrGln Gly Glu Ser Ser Asp 340 345 350 Ile Glu Val Lys Pro Gln Ala Thr GluThr Thr Glu Ala Ser Gln Tyr 355 360 365 Gly Pro Arg Pro Gln Phe Asn LysThr Pro Lys Tyr Val Lys Tyr Arg 370 375 380 Asp Ala Gly Thr Gly Ile ArgGlu Tyr Asn Asp Gly Thr Phe Gly Tyr 385 390 395 400 Glu Ala Arg Pro ArgPhe Asn Lys Pro Ser Glu Thr Asn Ala Tyr Asn 405 410 415 Val Thr Thr HisAla Asn Gly Gln Val Ser Tyr Gly Ala Arg Pro Thr 420 425 430 Tyr Lys LysPro Ser Glu Thr Asn Ala Tyr Asn Val Thr Thr His Ala 435 440 445 Asn GlyGln Val Ser Tyr Gly Ala Arg Pro Thr Gln Asn Lys Pro Ser 450 455 460 LysThr Asn Ala Tyr Asn Val Thr Thr His Gly Asn Gly Gln Val Ser 465 470 475480 Tyr Gly Ala Arg Gln Ala Gln Asn Lys Pro Ser Lys Thr Asn Ala Tyr 485490 495 Asn Val Thr Thr His Ala Asn Gly Gln Val Ser Tyr Gly Ala Arg Pro500 505 510 Thr Tyr Lys Lys Pro Ser Lys Thr Asn Ala Tyr Asn Val Thr ThrHis 515 520 525 Ala Asp Gly Thr Ala Thr Tyr Gly Pro Arg Val Thr Lys 530535 540 31 356 PRT Staphylococcus aureus 31 Met Lys Met Arg Thr Ile AlaLys Thr Ser Leu Ala Leu Gly Leu Leu 1 5 10 15 Thr Thr Gly Ala Ile ThrVal Thr Thr Gln Ser Val Lys Ala Glu Lys 20 25 30 Ile Gln Ser Thr Lys ValAsp Lys Val Pro Thr Leu Lys Ala Glu Arg 35 40 45 Leu Ala Met Ile Asn IleThr Ala Gly Ala Asn Ser Ala Thr Thr Gln 50 55 60 Ala Ala Asn Thr Arg GlnGlu Arg Thr Pro Lys Leu Glu Lys Ala Pro 65 70 75 80 Asn Thr Asn Glu GluLys Thr Ser Ala Ser Lys Ile Glu Lys Ile Ser 85 90 95 Gln Pro Lys Gln GluGlu Gln Lys Thr Leu Asn Ile Ser Ala Thr Pro 100 105 110 Ala Pro Lys GlnGlu Gln Ser Gln Thr Thr Thr Glu Ser Thr Thr Pro 115 120 125 Lys Thr LysVal Thr Thr Pro Pro Ser Thr Asn Thr Pro Gln Pro Met 130 135 140 Gln SerThr Lys Ser Asp Thr Pro Gln Ser Pro Thr Ile Lys Gln Ala 145 150 155 160Gln Thr Asp Met Thr Pro Lys Tyr Glu Asp Leu Arg Ala Tyr Tyr Thr 165 170175 Lys Pro Ser Phe Glu Phe Glu Lys Gln Phe Gly Phe Met Leu Lys Pro 180185 190 Trp Thr Thr Val Arg Phe Met Asn Val Ile Pro Asn Arg Phe Ile Tyr195 200 205 Lys Ile Ala Leu Val Gly Lys Asp Glu Lys Lys Tyr Lys Asp GlyPro 210 215 220 Tyr Asp Asn Ile Asp Val Phe Ile Val Leu Glu Asp Asn LysTyr Gln 225 230 235 240 Leu Lys Lys Tyr Ser Val Gly Gly Ile Thr Lys ThrAsn Ser Lys Lys 245 250 255 Val Asn His Lys Val Glu Leu Ser Ile Thr LysLys Asp Asn Gln Gly 260 265 270 Met Ile Ser Arg Asp Val Ser Glu Tyr MetIle Thr Lys Glu Glu Ile 275 280 285 Ser Leu Lys Glu Leu Asp Phe Lys LeuArg Lys Gln Leu Ile Glu Lys 290 295 300 His Asn Leu Tyr Gly Asn Met GlySer Gly Thr Ile Val Ile Lys Met 305 310 315 320 Lys Asn Gly Gly Lys TyrThr Phe Glu Leu His Lys Lys Leu Gln Glu 325 330 335 His Arg Met Ala AspVal Ile Asp Gly Thr Asn Ile Asp Asn Ile Glu 340 345 350 Val Asn Ile Lys355 32 313 PRT Staphylococcus aureus 32 Met Glu His Thr Thr Met Lys IleThr Thr Ile Ala Lys Thr Ser Leu 1 5 10 15 Ala Leu Gly Leu Leu Thr ThrGly Val Ile Thr Thr Thr Thr Gln Ala 20 25 30 Ala Asn Ala Thr Thr Leu SerSer Thr Lys Val Glu Ala Pro Gln Ser 35 40 45 Thr Pro Pro Ser Thr Lys IleGlu Ala Pro Gln Ser Lys Pro Asn Ala 50 55 60 Thr Thr Pro Pro Ser Thr LysVal Glu Ala Pro Gln Gln Thr Ala Asn 65 70 75 80 Ala Thr Thr Pro Pro SerThr Lys Val Thr Thr Pro Pro Ser Thr Asn 85 90 95 Thr Pro Gln Pro Met GlnSer Thr Lys Ser Asp Thr Pro Gln Ser Pro 100 105 110 Thr Thr Lys Gln ValPro Thr Glu Ile Asn Pro Lys Phe Lys Asp Leu 115 120 125 Arg Ala Tyr TyrThr Lys Pro Ser Leu Glu Phe Lys Asn Glu Ile Gly 130 135 140 Ile Ile LeuLys Lys Trp Thr Thr Ile Arg Phe Met Asn Val Val Pro 145 150 155 160 AspTyr Phe Ile Tyr Lys Ile Ala Leu Val Gly Lys Asp Asp Lys Lys 165 170 175Tyr Gly Glu Gly Val His Arg Asn Val Asp Val Phe Val Val Leu Glu 180 185190 Glu Asn Asn Tyr Asn Leu Glu Lys Tyr Ser Val Gly Gly Ile Thr Lys 195200 205 Ser Asn Ser Lys Lys Val Asp His Lys Ala Gly Val Arg Ile Thr Lys210 215 220 Glu Asp Asn Lys Gly Thr Ile Ser His Asp Val Ser Glu Phe LysIle 225 230 235 240 Thr Lys Glu Gln Ile Ser Leu Lys Glu Leu Asp Phe LysLeu Arg Lys 245 250 255 Gln Leu Ile Glu Lys Asn Asn Leu Tyr Gly Asn ValGly Ser Gly Lys 260 265 270 Ile Val Ile Lys Met Lys Asn Gly Gly Lys TyrThr Phe Glu Leu His 275 280 285 Lys Lys Leu Gln Glu Asn Arg Met Ala AspVal Ile Asp Gly Thr Asn 290 295 300 Ile Asp Asn Ile Glu Val Asn Ile Lys305 310

1. An isolated nucleic acid molecule comprising a DNA sequence selectedfrom the group consisting of: (i) the DNA sequence as represented in SEQID NO's 1-13; (ii) DNA sequences which hybridise to the sequencepresented in the SEQ ID No's 1-13 identified in (i) above and whichencode a polypeptide expressed by a pathogenic organism; and (iii) DNAsequences which are degenerate as a result of the genetic code to theDNA sequences defined in (i) and (ii).
 2. An isolated nucleic acidmolecule according to claim 1 which is genomic DNA.
 3. An isolatednucleic acid molecule according to claim 1 or 2 which anneals understringent hybridisation conditions to the sequences presented in SEQ IDNO's 1-13.
 4. A vector comprising a nucleic acid molecule according toany of claims 1-3.
 5. A vector according to claim 4 wherein the vectoris adapted for recombinant expression of the polypeptide encoded by thenucleic acid.
 6. A vector according to claim 4 or 5 wherein said vectoris an expression vector adapted for prokaryotic gene expression.
 7. Avector according to claim 4 or 5 wherein said vector is an expressionvector adapted for eukaryotic gene expression.
 8. A vector according toany of claims 4 to 7 wherein the adaptation of the vector includes theprovision of promoter sequences.
 9. A vector according to claim 8wherein the promoter sequences provide for cell specific, inducible orconstitutive expression.
 10. A method to identify antigenic polypeptidescomprising: (i) providing a nucleic acid library encoding genes orpartial gene sequences of a pathogenic organism; (ii)transforming/transfecting said library into a host cell; (iii)contacting the polypeptides expressed by the genes/partial genesequences with autologous antisera derived from an animal infected with,or has been infected with, said pathogenic organism; and (iv) purifyingthe nucleic acid encoding the polypeptide or partial polypeptide bindingto said autologous antisera.
 11. A method according to claim 10 whereinsaid library comprises genomic DNA of a pathogenic organism.
 12. Amethod according to claim 10 or claim 11 wherein said pathogenicorganism is bacterial.
 13. A method according to any of claims 10 to 12wherein said bacterial organism is selected from the following:Staphylococcus aureus; Staphylococcus epidermidis; Enterococcusfaecalis; Mycobacterium tuberculsis; Streptococcus group B;Streptoccocus pneumoniae; Helicobacter pylori; Neisseria gonorrhea;Streptococcus group A; Borrelia burgdorferi; Coccidiodes immitis;Histoplasma sapsulatum; Neisseria meningitidis type B; Shigellaflexneri; Escherichia coli; Haemophilus influenzae
 14. A methodaccording to any of claim 13 wherein said pathogenic organism isStaphylococcus aureus.
 15. A method according to any of claim 13 whereinsaid pathogenic organism is Staphylococcus epidermidis.
 16. A methodaccording to any of claims 10 to 15 wherein said nucleic acid library isa lambda library.
 17. A polypeptide identified by the method accordingto any of claims 10 to
 16. 18. A polypeptide according to claim 17 whichis selected from the group consisting of SEQ ID NO's: 14-19.
 19. Amethod for the production of the polypeptides according to any of claims17 or 18 comprising: (i) providing a cell transformed/transfected with avector according to any of claims 4 to 9 and with cell cultureconditions; and (ii) purifying said polypeptide from said cell, or itsgrowth environment.
 20. A method according to claim 19 wherein saidvector encodes, and thus said recombinant polypeptide is provided with,a secretion signal to facilitate purification of said polypeptide.
 21. Acell transformed or transfected with the vector according to any ofclaims 4 to
 9. 22. A cell according to claim 21 which is a prokaryoticcell.
 23. A cell according to claim 21 which is a eukaryotic cellselected from the group consisting of: fungal cell, insect cell,amphibian cell; mammalian cell; plant cell.
 24. A vaccine comprising atleast one polypeptide according to claims 16 or
 17. 25. A vaccineaccording to claim 24 which further comprises a carrier and/or adjuvant.26. A method to immunise an animal against a pathogenic microbecomprising administering to the animal at least one polypeptide, or partthereof, according to any previous claim or the vaccine of any previousclaim.
 27. A method according to claim 26 wherein the animal is human.28. A method according to claim 26 or 27 wherein the vaccine, orantigenic polypeptide, is delivered by direct injection eitherintravenously, intramuscularly or subcutaneously.
 29. A method accordingto claim 25 or 26 wherein the vaccine or antigenic polypeptide is takenorally.
 30. A method according to any of claims 26 to 29 wherein thevaccine is against the bacterial genus Staphylococcus spp.
 31. A methodaccording to claim 30 wherein the vaccine is against the bacterialspecies Staphylococcus aureus.
 32. A method according to claim 30wherein the vaccine is against the bacterial species Staphylococcusepidermidis.
 33. An antibody, or at least an effective part thereof,which binds at least with a selective part of the polypeptide accordingto claim 16 or
 17. 34. An antibody according to claim 33 which is amonoclonal antibody.
 35. An antibody according to claim 33 or 34 whereinsaid effective part comprises FAb fragments.
 36. An antibody accordingto any of claims 33 to 35 which is a chimeric antibody.
 37. An antibodyaccording to any of claims 33 to 35 which is a humanised antibody. 38.An antibody according to any of claims 33 to 37 wherein said antibody isprovided with a marker, label or tag.
 39. An antibody according to claim38 wherein said antibody is provided with a marker selected from a groupconsisting of: a radioactive label, a fluorescent label; an epitope tag.40. An antibody according to any of claims 34 to 39 which is produced asa fusion polypeptide.
 41. A vector which is adapted for the expressionof the antibodies according to any of claims 34-40.
 42. A cell which hasbeen transformed or transfected with the vector according to claim 41.43. A method for the production of the antibody according to any ofclaims 34 or 40 comprising: i) providing a cell transformed ortransfected with the vector according to claim 41 and with cell cultureconditions; and ii) purifying said antibody from said cell, or itsgrowth environment.
 44. A hybridoma cell line which produces an antibodyaccording to claim
 34. 45. Use of the antibodies according to any ofclaims 33 to 40 for the manufacture of a medicament for the treatment ofStaphylococcus aureus-associated septicaemia, food-poisoning or skindisorders.
 46. Use of the antibodies according to any of claims 33 to 40for the manufacture of a medicament for the treatment of Staphylococcusepidermidis-associated septicaemia, peritonitis or endocarditis
 47. Amethod for preparing a hybridoma cell-line producing monoclonalantibodies according to claim 34, comprising the steps of: i) immunisingan immunocompetent mammal with an immunogen comprising at least onepolypeptide having the amino acid sequence as set forward in SEQ ID No:14-19, or fragments thereof; ii) fusing lymphocytes of the immunisedimmunocompetent mammal with myeloma cells to form hybridoma cells; iii)screening monoclonal antibodies produced by the hybridoma cells of step(ii) for binding activity to the amino acid sequences of (i); iv)culturing the hybridoma cells to proliferate and/or to secrete saidmonoclonal antibody; and v) recovering the monoclonal antibody from theculture supernatant.
 48. A method according to claim 47, wherein saidimmunocompetent mammal is a mouse
 49. A method according to claim 47,wherein said immunocompetent mammal is a rat